# NM_000485.3(APRT):c.185C>T (p.Ala62Val)

https://sugi.bio/variant/aprt-p-ala62val

## Summary

**APRT p.Ala62Val (c.185C>T)** is classified **Benign** in APRT (ClinVar, Single submitter, 3 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.1264); Rare (popmax 0.648%, afr).

**At a glance:** Benign · review: Single submitter · rsID rs201579274 · 3 submitters · AlphaMissense likely benign · rare (popmax 0.648%, afr)

## For patients & families {#patients}

This is a change in the APRT gene that is classified as benign — not considered disease-causing, submitted by 3 submitters.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [APRT](https://sugi.bio/atlas/gene/APRT/) |
| Protein change (HGVS p.) | p.Ala62Val |
| Coding change (HGVS c.) | c.185C>T |
| MANE Select transcript | [NM_000485](https://www.ncbi.nlm.nih.gov/nuccore/NM_000485) |
| dbSNP | [rs201579274](https://www.ncbi.nlm.nih.gov/snp/rs201579274/) |
| Variant type | single nucleotide variant |
| Location | chr16:88811552-88811552 (GRCh38) |
| ClinVar | [VCV2070367](https://www.ncbi.nlm.nih.gov/clinvar/variation/2070367/) |

**All HGVS expressions:** `NC_000016.10:g.88811552G>A`, `NC_000016.9:g.88877960G>A`, `NG_008013.1:g.5383C>T`, `NM_000485.2:c.185C>T`, `NM_000485.3:c.185C>T`, `NM_001030018.2:c.185C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- AlphaMissense **likely benign** (0.1264)
- REVEL 0.51 (indeterminate)
- SaProt LLR -8.655 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense and SaProt both call this tolerated; REVEL makes no call
- SpliceAI predicts **donor gain** (Δ 0.24) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP 4.056, GERP 1.19, phastCons 1 — highly conserved (differs from AlphaMissense)
- CADD: **PHRED 20.8**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- Regional missense constraint: **o/e 1.26** across the covering region of the MANE Select transcript (88,809,701–88,811,899), spanning 2,198 bp. Chi-square p 5.8e-05. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI deltas (raw): acceptor loss **0.00**, donor loss **0.06**, acceptor gain **0.00**, donor gain **0.24**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.24**.
- Population frequency (gnomAD v4.1): grpmax **0.648%** (afr) · FAF95 0.601% · FAF99 0.582% · 484/74,636 in the highest group · 517/1,593,158 alleles overall — rare (popmax 0.648%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.648% | 154 |
| Remaining individuals (not grpmax-eligible) | 0.0324% | 3,083 |
| Admixed American | 0.0156% | 6,411 |
| South Asian | 0.00227% | 44,061 |
| European (non-Finnish) | 0.000171% | 585,648 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**APRT** population constraint: LOEUF 1.789, pLI 4.7393e-11, missense-Z -1.8254. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **62** lies in a β-strand.

AlphaFold model confidence (whole protein): pLDDT 96.91, 96% of residues very-high.

**16 experimental structure(s)** (PDB): [1ORE](https://www.rcsb.org/structure/1ORE), [1ZN7](https://www.rcsb.org/structure/1ZN7), [1ZN8](https://www.rcsb.org/structure/1ZN8), [1ZN9](https://www.rcsb.org/structure/1ZN9), [4X44](https://www.rcsb.org/structure/4X44), [4X45](https://www.rcsb.org/structure/4X45) — incl. mutant structure 4X44.

## What this gene does {#gene-function}

*Describes the biological roles of APRT (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** APRT's established molecular role includes adenine phosphoribosyltransferase activity. In Reactome, APRT is annotated in disease pathway(s) including **Defective APRT disrupts adenine salvage**.

**Disease mechanism (Reactome):** APRT loss or alteration is curated in [Defective APRT disrupts adenine salvage](https://reactome.org/content/detail/R-HSA-9734195).

### Pathways affected {#pathways}

APRT participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective APRT disrupts adenine salvage](https://reactome.org/content/detail/R-HSA-9734195) | curated |
| [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) | curated |
| [Purine salvage](https://reactome.org/content/detail/R-HSA-74217) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** adenine phosphoribosyltransferase activity, AMP binding.

## Clinical significance {#significance}

**Benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2026-01-06.

**Submitter consensus:** conflicting (1 Likely benign, 1 Benign).

**Submission history:** 3 submissions (2023–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Likely benign | no assertion criteria provided | clinical testing | 2023-10-30 |
| Dr. Peter K. Rogan Lab, Western University |  | no classification provided | in vitro |  |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-01-06 |

**Reported phenotype names (ClinVar):** not provided, APRT-related disorder, Clear cell carcinoma of kidney, none provided, APRT-related condition.

## Similar variants {#similar}

Related APRT variant pages (same residue, condition, or type): [APRT p.Arg67Gln](/variant/aprt-p-arg67gln), [APRT p.Arg67Ter](/variant/aprt-p-arg67ter), [APRT p.Arg87Ter](/variant/aprt-p-arg87ter), [APRT p.Asp65Val](/variant/aprt-p-asp65val), [APRT p.Gly133Arg](/variant/aprt-p-gly133arg), [APRT p.Gly63Asp](/variant/aprt-p-gly63asp), [APRT p.Met1Ile](/variant/aprt-p-met1ile), [APRT p.Met1Val](/variant/aprt-p-met1val).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2070367). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*