Is DMRT1 p.Val304Met (c.910G>A) pathogenic?

DMRT1 p.Val304Met (c.910G>A) is classified Likely benign in DMRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-16). AlphaMissense: likely benign (0.1003); Ultra-rare (popmax 0.0813%, afr).

How common is DMRT1 p.Val304Met (c.910G>A) in the general population?

DMRT1 p.Val304Met (c.910G>A) is ultra-rare (popmax 0.0813%, afr) (gnomAD).

What do computational predictors say about DMRT1 p.Val304Met (c.910G>A)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

DMRT1 p.Val304Met

c.910G>A · rs141672484 · VCV2710366

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2
Regional constraint	o/e 1.29	unconstrained · MANE · 121 kb · p 1.4e-07 · regional, not allelic
Overall
CADD	2.057	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0813% African / African-American · 61/75,030 alleles

Filtering AF 0.0649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.059%

Overall 0.00539% 87/1,614,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0813%	1,230
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.00439%	22,768
Admixed American	0.00333%	30,012
East Asian	0.00223%	44,884
European (non-Finnish)	0.00102%	98,335

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: DMRT1
Protein: p.Val304Met
Coding: c.910G>A
MANE Select: NM_021951
dbSNP: rs141672484
Type: single nucleotide variant
Location: chr9:916850 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB

Full DMRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT1 p.Asn151Ser Uncertain significance ★★ ⚠ same type
DMRT1 p.Met275Val Uncertain significance ★★ ⚠ same type
DMRT1 p.Ser58Cys Uncertain significance ★★ ⚠ same type
DMRT1 p.Thr366Ser Uncertain significance ★★ ⚠ same type
DMRT1 p.Val265Met Uncertain significance ★★ ⚠ same type
DMRT1 c.355-218G>C Benign ★★ same type
DMRT1 c.355-8G>C Benign ★★ same type
DMRT1 c.538+65A>G Benign ★★ 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/dmrt1-p-val304met (accessed [today's date]).

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