Is DMD p.Ala437Pro (c.1309G>C) pathogenic?

DMD p.Ala437Pro (c.1309G>C) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.928); Ultra-rare (popmax 0.0176%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala437Pro (c.1309G>C)?

DMD p.Ala437Pro (c.1309G>C) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala437Pro (c.1309G>C) in the general population?

DMD p.Ala437Pro (c.1309G>C) is ultra-rare (popmax 0.0176%, amr) (gnomAD).

What do computational predictors say about DMD p.Ala437Pro (c.1309G>C)?

AlphaMissense predicts likely pathogenic (score 0.928) — an in-silico prediction, not a clinical call.

DMD p.Ala437Pro

c.1309G>C · rs748964279 · VCV455860

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, amr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.928	likely pathogenic · top 10% in DMD
REVEL	0.246	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.7	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 0.0176% Admixed American · 8/45,439 alleles

Filtering AF 0.00874% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000912% 11/1,206,681 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0176%	5,680
Remaining individualsnot grpmax-eligible	0.00211%	47,483
European (non-Finnish)	0.000224%	446,714

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: DMD
Protein: p.Ala437Pro
Coding: c.1309G>C
MANE Select: NM_004006
dbSNP: rs748964279
Type: single nucleotide variant
Location: chrX:32644154 (GRCh38)
Residue 437: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Ala437Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
DMD p.Ala437Thr Uncertain significance ★★ ⚠ same residue
DMD p.Ala437= Likely benign ★★ same residue
DMD p.Ala437Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Ala437Val Uncertain significance ★ ⚠ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition

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/dmd-p-ala437pro (accessed [today's date]).

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