Is DALRD3 p.Ala14Pro (c.40G>C) pathogenic?

DALRD3 p.Ala14Pro (c.40G>C) is classified Uncertain significance in DALRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely pathogenic (0.6649); Very rare (popmax 0.00378%, nfe).

How common is DALRD3 p.Ala14Pro (c.40G>C) in the general population?

DALRD3 p.Ala14Pro (c.40G>C) is very rare (popmax 0.00378%, nfe) (gnomAD).

What do computational predictors say about DALRD3 p.Ala14Pro (c.40G>C)?

AlphaMissense predicts likely pathogenic (score 0.6649) — an in-silico prediction, not a clinical call.

DALRD3 p.Ala14Pro

c.40G>C · rs776886347 · VCV2461838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00378%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6649	likely pathogenic
REVEL	0.351	indeterminate
SaProt	LLR -10.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,973 bp · p 0.019 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00378% European (non-Finnish) · 44/1,164,644 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00284% 45/1,583,096 alleles · very rare exomes 45/1,430,718 · genomes 0/152,378 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00378%	26,469
Remaining individualsnot grpmax-eligible	0.00163%	61,172

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.Ala14Pro
Coding: c.40G>C
MANE Select: NM_001009996
dbSNP: rs776886347
Type: single nucleotide variant
Location: chr3:49018525 (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.Ala14Ser 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-ala14pro (accessed [today's date]).

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