Is DMRT2 p.Arg382Gln (c.1145G>A) pathogenic?

DMRT2 p.Arg382Gln (c.1145G>A) is classified Benign in DMRT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-19). AlphaMissense: likely benign (0.0702); Common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DMRT2 p.Arg382Gln (c.1145G>A)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

DMRT2 p.Arg382Gln

Q: How common is DMRT2 p.Arg382Gln (c.1145G>A) in the general population?

DMRT2 p.Arg382Gln (c.1145G>A) is common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1145G>A · rs72703237 · VCV776402

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.37	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 2.4	GERP -2.3, phastCons 0.028
Regional constraint	o/e 1.42	unconstrained · MANE · 5,656 bp · p 7.1e-31 · regional, not allelic
Overall
CADD	7.229	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 6.53% African / African-American · 4,896/74,960 alleles

Filtering AF 6.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.32%

Overall 0.383% 6,175/1,614,034 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.53%	15
Ashkenazi Jewishnot grpmax-eligible	0.649%	154
Middle Eastern	0.594%	168
Remaining individualsnot grpmax-eligible	0.502%	199
Admixed American	0.415%	241
European (non-Finnish)	0.0406%	2,464
South Asian	0.00988%	10,120

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: DMRT2
Protein: p.Arg382Gln
Coding: c.1145G>A
MANE Select: NM_181872
dbSNP: rs72703237
Type: single nucleotide variant
Location: chr9:1056732 (GRCh38)
Gene constraint: LOEUF 1.279 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.37

Full DMRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT2 p.Ala112Glu Uncertain significance ★★ ⚠ same type
DMRT2 p.Ala29Ser Uncertain significance ★★ ⚠ same type
DMRT2 p.Asp176Gly Uncertain significance ★★ ⚠ same type
DMRT2 p.Asp48Glu Uncertain significance ★★ ⚠ same type
DMRT2 p.Cys105Tyr Uncertain significance ★★ ⚠ same type
DMRT2 p.Glu60Gln Uncertain significance ★★ ⚠ same type
DMRT2 p.Gly110Asp Uncertain significance ★★ ⚠ same type
DMRT2 p.Gly36Arg 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/dmrt2-p-arg382gln (accessed [today's date]).

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