Is DMRTC2 p.Asp303Val (c.908A>T) pathogenic?

DMRTC2 p.Asp303Val (c.908A>T) is classified Uncertain significance in DMRTC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: ambiguous (0.3743); Ultra-rare (popmax 0.0406%, sas).

How common is DMRTC2 p.Asp303Val (c.908A>T) in the general population?

DMRTC2 p.Asp303Val (c.908A>T) is ultra-rare (popmax 0.0406%, sas) (gnomAD).

What do computational predictors say about DMRTC2 p.Asp303Val (c.908A>T)?

AlphaMissense predicts ambiguous (score 0.3743) — an in-silico prediction, not a clinical call.

DMRTC2 p.Asp303Val

c.908A>T · rs782752150 · VCV2272834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3743 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3743	ambiguous
REVEL	0.143	moderately benign-leaning
SaProt	LLR -4.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 4,264 bp · p 0.055 · regional, not allelic
Overall
CADD	24.1	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 0.0406% South Asian · 37/91,030 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.00298% 48/1,613,420 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,460
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.000848%	117,985

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: DMRTC2
Protein: p.Asp303Val
Coding: c.908A>T
MANE Select: NM_001040283
dbSNP: rs782752150
Type: single nucleotide variant
Location: chr19:41850617 (GRCh38)
Gene constraint: LOEUF 0.521 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 60.70

Full DMRTC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRTC2 p.Ala202Thr Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala280Val Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala295Thr Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala307Ser Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala350Val Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala35Val Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala65Ser Uncertain significance ★ ⚠ same type
DMRTC2 p.Ala93Val 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/dmrtc2-p-asp303val (accessed [today's date]).

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