Is DMRT1 p.Pro261= (c.783C>T) pathogenic?

DMRT1 p.Pro261= (c.783C>T) is classified Benign in DMRT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-18). Common (popmax 5.72%, afr) — too common for a highly-penetrant pathogenic allele.

DMRT1 p.Pro261=

Q: How common is DMRT1 p.Pro261= (c.783C>T) in the general population?

DMRT1 p.Pro261= (c.783C>T) is common (popmax 5.72%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.783C>T · rs34946058 · VCV713511

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.72%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP -5.7
Overall
CADD	0.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.72% African / African-American · 4,293/75,058 alleles

Filtering AF 5.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.52%

Overall 0.309% 4,980/1,614,034 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.72%	17
Remaining individualsnot grpmax-eligible	0.427%	234
Admixed American	0.416%	240
Middle Eastern	0.187%	536
European (non-Finnish)	0.0124%	8,083
South Asian	0.011%	9,108
East Asian	0.00669%	14,957

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.Pro261=
Coding: c.783C>T
MANE Select: NM_021951
dbSNP: rs34946058
Type: single nucleotide variant
Location: chr9:894156 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB

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

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-pro261 (accessed [today's date]).

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