Is DMRT1 p.Ala65Val (c.194C>T) pathogenic?

DMRT1 p.Ala65Val (c.194C>T) is classified Uncertain significance in DMRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.0987); Ultra-rare (popmax 0.0965%, mid).

How common is DMRT1 p.Ala65Val (c.194C>T) in the general population?

DMRT1 p.Ala65Val (c.194C>T) is ultra-rare (popmax 0.0965%, mid) (gnomAD).

What do computational predictors say about DMRT1 p.Ala65Val (c.194C>T)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

DMRT1 p.Ala65Val

c.194C>T · rs564444409 · VCV2369248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0965%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.30	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 4.5	GERP 2.2, phastCons 0.39
Regional constraint	o/e 1.32	unconstrained · MANE · 316 bp · p 7e-05 · regional, not allelic
Overall
CADD	18.37	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 0.0965% Middle Eastern · 5/5,182 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00355% 55/1,547,530 alleles · ultra-rare exomes 50/1,395,276 · genomes 5/152,254 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0965%	1,036
African / African-American	0.0313%	3,190
Remaining individualsnot grpmax-eligible	0.00832%	12,019
Admixed American	0.00194%	51,414
European (non-Finnish)	0.00183%	54,723

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.Ala65Val
Coding: c.194C>T
MANE Select: NM_021951
dbSNP: rs564444409
Type: single nucleotide variant
Location: chr9:842032 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB
Residue 65: the 'disordered' region

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

Similar variants

DMRT1 p.Ala65Gly Uncertain significance ★ ⚠ same residue
DMRT1 p.Ala65Ser Uncertain significance ★ ⚠ same residue
DMRT1 p.Ala65= Likely benign ★ same residue
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

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-ala65val (accessed [today's date]).

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