Is DMRT2 p.Ala150Ser (c.448G>T) pathogenic?

DMRT2 p.Ala150Ser (c.448G>T) is classified Likely benign in DMRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: ambiguous (0.405); Rare (popmax 0.12%, amr).

How common is DMRT2 p.Ala150Ser (c.448G>T) in the general population?

DMRT2 p.Ala150Ser (c.448G>T) is rare (popmax 0.12%, amr) (gnomAD).

What do computational predictors say about DMRT2 p.Ala150Ser (c.448G>T)?

AlphaMissense predicts ambiguous (score 0.405) — an in-silico prediction, not a clinical call.

DMRT2 p.Ala150Ser

c.448G>T · rs369093745 · VCV1645286

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.405 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.405	ambiguous
REVEL	0.209	benign-leaning
SaProt	LLR -9.47	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 5,656 bp · p 7.1e-31 · regional, not allelic
Overall
CADD	26.8	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 0.12% Admixed American · 50/41,640 alleles

Filtering AF 0.0936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0841%

Overall 0.00361% 53/1,468,832 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.12%	833
European (non-Finnish)	0.000269%	372,096

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: DMRT2
Protein: p.Ala150Ser
Coding: c.448G>T
MANE Select: NM_181872
dbSNP: rs369093745
Type: single nucleotide variant
Location: chr9:1052061 (GRCh38)
Gene constraint: LOEUF 1.279 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.37
Residue 150: a DNA-binding region

Full DMRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT2 p.Ala150Thr Uncertain significance ★ ⚠ same residue
DMRT2 p.Ala112Glu Uncertain significance ★★ ⚠ same type
DMRT2 p.Ala29Ser Uncertain significance ★★ ⚠ same type
DMRT2 p.Asp176Gly Uncertain significance ★★ ⚠ same type
DMRT2 p.Asp48Glu Uncertain significance ★★ ⚠ same type
DMRT2 p.Cys105Tyr Uncertain significance ★★ ⚠ same type
DMRT2 p.Glu60Gln Uncertain significance ★★ ⚠ same type
DMRT2 p.Gly110Asp 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/dmrt2-p-ala150ser (accessed [today's date]).

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