Is DALRD3 p.Val247Ala (c.740T>C) pathogenic?

DALRD3 p.Val247Ala (c.740T>C) is classified Uncertain significance in DALRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.112); Very rare (popmax 0.00167%, amr).

How common is DALRD3 p.Val247Ala (c.740T>C) in the general population?

DALRD3 p.Val247Ala (c.740T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DALRD3 p.Val247Ala (c.740T>C)?

AlphaMissense predicts likely benign (score 0.112) — an in-silico prediction, not a clinical call.

DALRD3 p.Val247Ala

c.740T>C · rs760225287 · VCV2618243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.112	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.18	GERP -3.3
Regional constraint	o/e 1.09	unconstrained · MANE · 2,973 bp · p 0.019 · regional, not allelic
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,022 alleles

Overall 0.000186% 3/1,614,144 alleles · very rare exomes 3/1,461,788 · genomes 0/152,356 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	8.47e-05%	1,180,044

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DALRD3
Protein: p.Val247Ala
Coding: c.740T>C
MANE Select: NM_001009996
dbSNP: rs760225287
Type: single nucleotide variant
Location: chr3:49017492 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57

Full DALRD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DALRD3 p.Val247Met Uncertain significance ★ ⚠ same residue
DALRD3 c.1512+18T>C Benign ★★ same type
DALRD3 p.Gln299Arg Benign ★★ same type
DALRD3 p.Gln299Ter Likely pathogenic ★ same type
DALRD3 c.1329+1G>A Uncertain significance ★ same type
DALRD3 c.-5T>C Uncertain significance ★ same type
DALRD3 p.Ala109Ser Uncertain significance ★ ⚠ same type
DALRD3 p.Ala149Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dalrd3-p-val247ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown