Is DMRT3 p.Ser463Pro (c.1387T>C) pathogenic?

DMRT3 p.Ser463Pro (c.1387T>C) is classified Benign in DMRT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-19). AlphaMissense: likely benign (0.2986); Low-frequency (popmax 1.22%, afr).

How common is DMRT3 p.Ser463Pro (c.1387T>C) in the general population?

DMRT3 p.Ser463Pro (c.1387T>C) is low-frequency (popmax 1.22%, afr) (gnomAD).

What do computational predictors say about DMRT3 p.Ser463Pro (c.1387T>C)?

AlphaMissense predicts likely benign (score 0.2986) — an in-silico prediction, not a clinical call.

DMRT3 p.Ser463Pro

c.1387T>C · rs151108780 · VCV783539

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2986 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2986	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -7.10	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 1.5	GERP 0.67, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 14 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	19.79	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 1.22% African / African-American · 917/75,010 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.0654% 1,055/1,613,924 alleles · low-frequency exomes 551/1,461,676 · genomes 504/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.22%	82
Remaining individualsnot grpmax-eligible	0.101%	992
Admixed American	0.0916%	1,091
Middle Eastern	0.033%	3,030
South Asian	0.00549%	18,211
European (non-Finnish)	0.0011%	90,763

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.Ser463Pro
Coding: c.1387T>C
MANE Select: NM_021240
dbSNP: rs151108780
Type: single nucleotide variant
Location: chr9:990973 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.72
Residue 463: the 'disordered' region

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.Pro18Gln Benign ★★ same type
DMRT3 p.Pro98= 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-ser463pro (accessed [today's date]).

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