Is DMRT1 p.Arg111Met (c.332G>T) pathogenic?

DMRT1 p.Arg111Met (c.332G>T) is classified Likely pathogenic in DMRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-02-27). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with 46,XY sex reversal 4.

What condition is associated with DMRT1 p.Arg111Met (c.332G>T)?

DMRT1 p.Arg111Met (c.332G>T) is associated with 46,XY sex reversal 4 (ClinVar).

How common is DMRT1 p.Arg111Met (c.332G>T) in the general population?

DMRT1 p.Arg111Met (c.332G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMRT1 p.Arg111Met (c.332G>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

DMRT1 p.Arg111Met

c.332G>T · rs1057519638 · VCV393463

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,544,312)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

46,XY sex reversal 4

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 1% in DMRT1
REVEL	0.578	indeterminate
SaProt	LLR -16.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 4,823 bp · p 0.00026 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,544,312). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DMRT1
Protein: p.Arg111Met
Coding: c.332G>T
MANE Select: NM_021951
dbSNP: rs1057519638
Type: single nucleotide variant
Location: chr9:842170 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB
Residue 111: a DNA-binding region

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

Disease context

46,XY sex reversal 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg111met (accessed [today's date]).

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