Is DMD p.Ala1065Pro (c.3193G>C) pathogenic?

DMD p.Ala1065Pro (c.3193G>C) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.7131); Ultra-rare (popmax 0.0178%, eas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala1065Pro (c.3193G>C)?

DMD p.Ala1065Pro (c.3193G>C) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala1065Pro (c.3193G>C) in the general population?

DMD p.Ala1065Pro (c.3193G>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DMD p.Ala1065Pro (c.3193G>C)?

AlphaMissense predicts likely pathogenic (score 0.7131) — an in-silico prediction, not a clinical call.

DMD p.Ala1065Pro

c.3193G>C · rs774756042 · VCV967009

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7131	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 6/33,720 alleles

Filtering AF 0.00767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00528%

Overall 0.000498% 6/1,205,859 alleles · ultra-rare exomes 3/1,094,194 · genomes 3/111,665 · joint denominator

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.Ala1065Pro
Coding: c.3193G>C
MANE Select: NM_004006
dbSNP: rs774756042
Type: single nucleotide variant
Location: chrX:32464669 (GRCh38)

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.Ala1065= Likely benign ★ same residue
DMD p.Ala1065fs Pathogenic ★ 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
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10223+1G>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-ala1065pro (accessed [today's date]).

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