Is DMRT3 p.Pro14Arg (c.41C>G) pathogenic?

DMRT3 p.Pro14Arg (c.41C>G) is classified Uncertain significance in DMRT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: ambiguous (0.53); Very rare (popmax 0.0038%, nfe).

How common is DMRT3 p.Pro14Arg (c.41C>G) in the general population?

DMRT3 p.Pro14Arg (c.41C>G) is very rare (popmax 0.0038%, nfe) (gnomAD).

What do computational predictors say about DMRT3 p.Pro14Arg (c.41C>G)?

AlphaMissense predicts ambiguous (score 0.53) — an in-silico prediction, not a clinical call.

DMRT3 p.Pro14Arg

c.41C>G · rs1301228434 · VCV3083134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.53 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0038%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.53	ambiguous
REVEL	0.265	benign-leaning
SaProt	LLR -7.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -0.2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 14 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	27.3	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 0.0038% European (non-Finnish) · 44/1,157,310 alleles

Filtering AF 0.00288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00257%

Overall 0.00294% 46/1,564,714 alleles · very rare exomes 42/1,412,684 · genomes 4/152,030 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0038%	26,302
South Asian	0.00233%	42,929

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.Pro14Arg
Coding: c.41C>G
MANE Select: NM_021240
dbSNP: rs1301228434
Type: single nucleotide variant
Location: chr9:977042 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.72

Full DMRT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMRT3 p.Pro14= Likely benign ★ same residue
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.Ser463Pro Benign ★★ same type
DMRT3 p.Val424Ile Likely benign ★★ same type
DMRT3 p.Pro443Ser Likely pathogenic ★ ⚠ 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-pro14arg (accessed [today's date]).

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