# NM_001009996.3(DALRD3):c.249G>A (p.Ala83=)

https://sugi.bio/variant/dalrd3-p-ala83

## Summary

**DALRD3 p.Ala83= (c.249G>A)** is classified **Likely benign** in DALRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 0.000181%, nfe).

**At a glance:** Likely benign · review: Single submitter · rsID rs2471601640 · 1 submitter · very rare (popmax 0.000181%, nfe)

## For patients & families {#patients}

This is a change in the DALRD3 gene that is classified as likely benign — not considered disease-causing, 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 | [DALRD3](https://sugi.bio/atlas/gene/DALRD3/) |
| Protein change (HGVS p.) | p.Ala83= |
| Coding change (HGVS c.) | c.249G>A |
| MANE Select transcript | [NM_001009996](https://www.ncbi.nlm.nih.gov/nuccore/NM_001009996) |
| dbSNP | [rs2471601640](https://www.ncbi.nlm.nih.gov/snp/rs2471601640/) |
| Variant type | single nucleotide variant |
| Location | chr3:49018235-49018235 (GRCh38) |
| ClinVar | [VCV2653815](https://www.ncbi.nlm.nih.gov/clinvar/variation/2653815/) |

**All HGVS expressions:** `NC_000003.11:g.49055668C>T`, `NC_000003.12:g.49018235C>T`, `NG_016282.1:g.2761C>T`, `NG_033126.1:g.7837G>A`, `NM_001009996.3:c.249G>A`, `NM_001276405.2:c.249G>A`, `NM_018114.6:c.-253G>A`

## Computational & population evidence {#evidence}

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

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor gain** (Δ 0.33) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -0.858, GERP -3.99, phastCons 0.004 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 15.26**. 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.*
- SpliceAI deltas (raw): acceptor loss **0.06**, donor loss **0.00**, acceptor gain **0.04**, donor gain **0.33**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.04**, donor gain **0.33**.
- Population frequency (gnomAD v4.1): grpmax **0.000181%** (nfe) · FAF95 3e-05% · FAF99 1.1e-05% · 2/1,104,492 in the highest group · 2/1,438,096 alleles overall — very rare (popmax 0.000181%, 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}

**DALRD3** population constraint: LOEUF 1.126, pLI 1.0027e-14, missense-Z -1.6847. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.57, 66% of residues very-high.

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

*Describes the biological roles of DALRD3 (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:** DALRD3's established molecular role includes tRNA binding.


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

**Molecular function:** tRNA binding.

**Biological process:** tRNA C3-cytosine methylation.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-10-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2023-10-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related DALRD3 variant pages (same residue, condition, or type): [DALRD3 c.1512+18T>C](/variant/dalrd3-c-1512-plus-18t-c), [DALRD3 p.Gln299Arg](/variant/dalrd3-p-gln299arg), [DALRD3 p.Gln299Ter](/variant/dalrd3-p-gln299ter), [DALRD3 c.1329+1G>A](/variant/dalrd3-c-1329-plus-1g-a), [DALRD3 c.-5T>C](/variant/dalrd3-c-minus-5t-c), [DALRD3 p.Ala109Ser](/variant/dalrd3-p-ala109ser), [DALRD3 p.Ala149Ser](/variant/dalrd3-p-ala149ser), [DALRD3 p.Ala14Pro](/variant/dalrd3-p-ala14pro).

### 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 2653815). 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.*