# NM_024096.2(DCTPP1):c.5C>T (p.Ser2Phe)

https://sugi.bio/variant/dctpp1-p-ser2phe

## Summary

**DCTPP1 p.Ser2Phe (c.5C>T)** is classified **Uncertain significance** in DCTPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.2126); Very rare (popmax 0.000694%, nfe).

**At a glance:** Uncertain significance · review: Single submitter · rsID rs754320814 · 1 submitter · AlphaMissense likely benign · very rare (popmax 0.000694%, nfe)

## For patients & families {#patients}

This is a change in the DCTPP1 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*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 | [DCTPP1](https://sugi.bio/atlas/gene/DCTPP1/) |
| Protein change (HGVS p.) | p.Ser2Phe |
| Coding change (HGVS c.) | c.5C>T |
| MANE Select transcript | [NM_024096](https://www.ncbi.nlm.nih.gov/nuccore/NM_024096) |
| dbSNP | [rs754320814](https://www.ncbi.nlm.nih.gov/snp/rs754320814/) |
| Variant type | single nucleotide variant |
| Location | chr16:30429976-30429976 (GRCh38) |
| ClinVar | [VCV2615446](https://www.ncbi.nlm.nih.gov/clinvar/variation/2615446/) |

**All HGVS expressions:** `NC_000016.10:g.30429976G>A`, `NC_000016.9:g.30441297G>A`, `NG_193255.1:g.189G>A`, `NM_024096.2:c.5C>T`, `NR_134470.2:n.55C>T`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.2126)
- REVEL 0.288 (benign-leaning) — agrees with AlphaMissense
- SaProt LLR -10.239 (damaging) — differs from AlphaMissense
- → **In-silico consensus:** SaProt calls this damaging; AlphaMissense and REVEL do not
- Conservation: phyloP 3.94, GERP 1.81, phastCons 1 — highly conserved (differs from AlphaMissense)
- CADD: **PHRED 22.6**. 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 1.00** across the covering region of the MANE Select transcript (30,424,236–30,429,980), spanning 5,744 bp. Chi-square p 0.97. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (G>T, Δ0.29 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.000694%** (nfe) · FAF95 0.000299% · FAF99 0.000216% · 8/1,152,494 in the highest group · 8/1,557,026 alleles overall — very rare (popmax 0.000694%, nfe).

*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}

**DCTPP1** population constraint: LOEUF 1.458, pLI 0.0001147, missense-Z 0.15147. *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 **2** lies in a modified residue (n-acetylserine); a modified residue (phosphoserine); the 'disordered' region.

AlphaFold model confidence (whole protein): pLDDT 85.40, 71% of residues very-high.

**5 experimental structure(s)** (PDB): [7MU5](https://www.rcsb.org/structure/7MU5), [9YSM](https://www.rcsb.org/structure/9YSM), [9YSN](https://www.rcsb.org/structure/9YSN), [9YSO](https://www.rcsb.org/structure/9YSO), [9YSP](https://www.rcsb.org/structure/9YSP).

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

*Describes the biological roles of DCTPP1 (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:** DCTPP1's established molecular role includes identical protein binding. p.Ser2Phe falls in the disordered region.


### Pathways affected {#pathways}

DCTPP1 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Interconversion of nucleotide di- and triphosphates](https://reactome.org/content/detail/R-HSA-499943) | other |

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

**Molecular function:** identical protein binding, nucleoside triphosphate diphosphatase activity, dCTP diphosphatase activity.

**Biological process:** dCTP catabolic process, nucleoside triphosphate catabolic process, DNA protection.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-08-02.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-08-02 |

**Reported phenotype names (ClinVar):** not specified, AllHighlyPenetrant.

## Similar variants {#similar}

Related DCTPP1 variant pages (same residue, condition, or type): [DCTPP1 p.Ala18Pro](/variant/dctpp1-p-ala18pro), [DCTPP1 p.Arg109Cys](/variant/dctpp1-p-arg109cys), [DCTPP1 p.Arg111Cys](/variant/dctpp1-p-arg111cys), [DCTPP1 p.Arg126Trp](/variant/dctpp1-p-arg126trp), [DCTPP1 p.Arg135Cys](/variant/dctpp1-p-arg135cys), [DCTPP1 p.Arg135His](/variant/dctpp1-p-arg135his), [DCTPP1 p.Arg22Trp](/variant/dctpp1-p-arg22trp), [DCTPP1 p.Arg35Cys](/variant/dctpp1-p-arg35cys).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2026-10-14); 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 2615446). 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.*