Is DMRT2 p.Pro41Arg (c.122C>G) pathogenic?

DMRT2 p.Pro41Arg (c.122C>G) is classified Uncertain significance in DMRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-18). AlphaMissense: likely benign (0.0798); No allele count reported in gnomAD v4.1 (AN 1,534,090).

How common is DMRT2 p.Pro41Arg (c.122C>G) in the general population?

DMRT2 p.Pro41Arg (c.122C>G) is no allele count reported in gnomAD v4.1 (AN 1,534,090) (gnomAD).

What do computational predictors say about DMRT2 p.Pro41Arg (c.122C>G)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

DMRT2 p.Pro41Arg

c.122C>G · rs973254777 · VCV1469904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,090)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.15	GERP -0.22
Regional constraint	o/e 1.42	unconstrained · MANE · 5,656 bp · p 7.1e-31 · regional, not allelic
Overall
CADD	12.53	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

No allele count reported in gnomAD v4.1 (AN 1,534,090). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DMRT2
Protein: p.Pro41Arg
Coding: c.122C>G
MANE Select: NM_181872
dbSNP: rs973254777
Type: single nucleotide variant
Location: chr9:1051735 (GRCh38)
Gene constraint: LOEUF 1.279 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.37
Residue 41: the 'disordered' region

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

Similar variants

DMRT2 p.Pro41Ala Uncertain significance ★★ ⚠ same residue
DMRT2 p.Pro41= Likely benign ★ same residue
DMRT2 p.Pro41_Ala42insPro Uncertain significance same residue
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

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-pro41arg (accessed [today's date]).

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