Is DMRT1 p.Pro71Arg (c.212C>G) pathogenic?

DMRT1 p.Pro71Arg (c.212C>G) is classified Uncertain significance in DMRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely pathogenic (0.7364); Very rare (popmax 0.00273%, afr).

How common is DMRT1 p.Pro71Arg (c.212C>G) in the general population?

DMRT1 p.Pro71Arg (c.212C>G) is very rare (popmax 0.00273%, afr) (gnomAD).

What do computational predictors say about DMRT1 p.Pro71Arg (c.212C>G)?

AlphaMissense predicts likely pathogenic (score 0.7364) — an in-silico prediction, not a clinical call.

DMRT1 p.Pro71Arg

c.212C>G · rs1171421770 · VCV2831506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00273%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7364	likely pathogenic
REVEL	0.24	benign-leaning
SaProt	LLR -10.45	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 316 bp · p 7e-05 · regional, not allelic
Overall
CADD	28.7	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 0.00273% African / African-American · 2/73,310 alleles

Filtering AF 0.000453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000169%

Overall 0.000574% 8/1,393,128 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00273%	36,655
European (non-Finnish)	0.000522%	191,424

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.Pro71Arg
Coding: c.212C>G
MANE Select: NM_021951
dbSNP: rs1171421770
Type: single nucleotide variant
Location: chr9:842050 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB
Residue 71: the 'disordered' region

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

Similar variants

DMRT1 p.Pro71= 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
DMRT1 c.355-218G>C Benign ★★ same type
DMRT1 c.355-8G>C 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-pro71arg (accessed [today's date]).

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