Is DMRTA2 p.Pro485Arg (c.1454C>G) pathogenic?

DMRTA2 p.Pro485Arg (c.1454C>G) is classified Uncertain significance in DMRTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely pathogenic (0.9611); Very rare (popmax 0.00536%, amr).

How common is DMRTA2 p.Pro485Arg (c.1454C>G) in the general population?

DMRTA2 p.Pro485Arg (c.1454C>G) is very rare (popmax 0.00536%, amr) (gnomAD).

What do computational predictors say about DMRTA2 p.Pro485Arg (c.1454C>G)?

AlphaMissense predicts likely pathogenic (score 0.9611) — an in-silico prediction, not a clinical call.

DMRTA2 p.Pro485Arg

c.1454C>G · VCV3502721

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9611 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00536%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9611	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -9.60	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 0.99, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,497 bp · p 0.091 · regional, not allelic
Overall
CADD	26.2	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 0.00536% Admixed American · 3/56,002 alleles

Filtering AF 0.00142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000694%

Overall 0.00021% 3/1,425,572 alleles · very rare

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: DMRTA2
Protein: p.Pro485Arg
Coding: c.1454C>G
MANE Select: NM_032110
Type: single nucleotide variant
Location: chr1:50418840 (GRCh38)
Gene constraint: LOEUF 1.236 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.64

Full DMRTA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRTA2 p.Pro485Ser Uncertain significance ★ ⚠ same residue
DMRTA2 p.Leu406Gln Uncertain significance ★★ ⚠ same type
DMRTA2 p.Ala394= Benign ★★ same type
DMRTA2 p.Ala396= Benign ★★ same type
DMRTA2 p.Ser477Asn Benign/Likely benign ★★ ⚠ same type
DMRTA2 p.Ala144Thr Uncertain significance ★ ⚠ same type
DMRTA2 p.Ala14Glu Uncertain significance ★ ⚠ same type
DMRTA2 p.Ala253Pro 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/dmrta2-p-pro485arg (accessed [today's date]).

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