Is DMRT1 p.Ser45Thr (c.133T>A) pathogenic?

DMRT1 p.Ser45Thr (c.133T>A) is classified Benign in DMRT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0904); Common (popmax 47.6%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DMRT1 p.Ser45Thr (c.133T>A)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

DMRT1 p.Ser45Thr

Q: How common is DMRT1 p.Ser45Thr (c.133T>A) in the general population?

DMRT1 p.Ser45Thr (c.133T>A) is common (popmax 47.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.133T>A · rs3739583 · VCV1280947

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 47.6%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.91	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 0.47	GERP -3, phastCons 0.006
Regional constraint	o/e 1.32	unconstrained · MANE · 316 bp · p 7e-05 · regional, not allelic
Overall
CADD	5.303	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 47.6% East Asian · 20,766/43,630 alleles

Filtering AF 47.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.8%

Overall 15.3% 242,894/1,583,340 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	47.6%	2
South Asian	25.2%	4
Ashkenazi Jewishnot grpmax-eligible	20.6%	5
Admixed American	18.8%	5
Middle Eastern	17.3%	6
Remaining individualsnot grpmax-eligible	17.1%	6
Amishnot grpmax-eligible	15.2%	7
European (non-Finnish)	13.5%	7
African / African-American	10.7%	9
Finnishnot grpmax-eligible	10.3%	10

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.Ser45Thr
Coding: c.133T>A
MANE Select: NM_021951
dbSNP: rs3739583
Type: single nucleotide variant
Location: chr9:841971 (GRCh38)
Gene constraint: LOEUF 0.432 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.76 · 1 PDB
Residue 45: a UniProt-annotated variant site (in); 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-ser45thr (accessed [today's date]).

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