Is DMRT3 p.Pro18Gln (c.53C>A) pathogenic?

DMRT3 p.Pro18Gln (c.53C>A) is classified Benign in DMRT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1369); Low-frequency (popmax 2.57%, afr).

How common is DMRT3 p.Pro18Gln (c.53C>A) in the general population?

DMRT3 p.Pro18Gln (c.53C>A) is low-frequency (popmax 2.57%, afr) (gnomAD).

What do computational predictors say about DMRT3 p.Pro18Gln (c.53C>A)?

AlphaMissense predicts likely benign (score 0.1369) — an in-silico prediction, not a clinical call.

DMRT3 p.Pro18Gln

c.53C>A · rs116052222 · VCV720431

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1369 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.57%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1369	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.04	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 5.6	GERP 0.77, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 14 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	24.7	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 2.57% African / African-American · 1,885/73,348 alleles

Filtering AF 2.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.43%

Overall 0.131% 2,061/1,571,990 alleles · low-frequency exomes 998/1,419,762 · genomes 1,063/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.57%	39
Admixed American	0.147%	678
Remaining individualsnot grpmax-eligible	0.135%	739
Middle Eastern	0.0209%	4,778
South Asian	0.00116%	86,570
European (non-Finnish)	0.00103%	96,709

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: DMRT3
Protein: p.Pro18Gln
Coding: c.53C>A
MANE Select: NM_021240
dbSNP: rs116052222
Type: single nucleotide variant
Location: chr9:977054 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.72

Full DMRT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT3 p.Arg217Cys Likely benign ★★ same type
DMRT3 p.Asn261Thr Benign ★★ same type
DMRT3 p.Pro98= Benign ★★ same type
DMRT3 p.Ser463Pro Benign ★★ same type
DMRT3 p.Val424Ile Likely benign ★★ same type
DMRT3 p.Pro443Ser Likely pathogenic ★ ⚠ same type
DMRT3 p.Ala103Thr Uncertain significance ★ ⚠ same type
DMRT3 p.Ala106Asp 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/dmrt3-p-pro18gln (accessed [today's date]).

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