Is DMRT1 p.Pro10Ser (c.28C>T) pathogenic?

DMRT1 p.Pro10Ser (c.28C>T) is classified Uncertain significance in DMRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-23). AlphaMissense: likely benign (0.0765); Ultra-rare (popmax 0.0481%, afr).

How common is DMRT1 p.Pro10Ser (c.28C>T) in the general population?

DMRT1 p.Pro10Ser (c.28C>T) is ultra-rare (popmax 0.0481%, afr) (gnomAD).

What do computational predictors say about DMRT1 p.Pro10Ser (c.28C>T)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

DMRT1 p.Pro10Ser

c.28C>T · rs139583942 · VCV2746267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.056	GERP -3.2, phastCons 0.92
Regional constraint	o/e 1.32	unconstrained · MANE · 316 bp · p 7e-05 · regional, not allelic
Overall
CADD	9.332	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% African / African-American · 36/74,922 alleles

Filtering AF 0.0357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00558% 90/1,612,684 alleles · ultra-rare exomes 69/1,460,438 · genomes 21/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0481%	2,081
Remaining individualsnot grpmax-eligible	0.00801%	12,477
European (non-Finnish)	0.00407%	24,575
Admixed American	0.00167%	59,936

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.Pro10Ser
Coding: c.28C>T
MANE Select: NM_021951
dbSNP: rs139583942
Type: single nucleotide variant
Location: chr9:841866 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB
Residue 10: the 'disordered' region

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-pro10ser (accessed [today's date]).

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