Is DMD p.Ala2953Asp (c.8858C>A) pathogenic?

DMD p.Ala2953Asp (c.8858C>A) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-31). AlphaMissense: likely pathogenic (0.7459); Very rare (popmax 0.00218%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala2953Asp (c.8858C>A)?

DMD p.Ala2953Asp (c.8858C>A) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala2953Asp (c.8858C>A) in the general population?

DMD p.Ala2953Asp (c.8858C>A) is very rare (popmax 0.00218%, amr) (gnomAD).

What do computational predictors say about DMD p.Ala2953Asp (c.8858C>A)?

AlphaMissense predicts likely pathogenic (score 0.7459) — an in-silico prediction, not a clinical call.

DMD p.Ala2953Asp

c.8858C>A · rs773941387 · VCV571602

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7459 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7459	likely pathogenic
REVEL	0.652	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.80 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00218% Admixed American · 1/45,916 alleles

Filtering AF 0.000384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000911% 10/1,097,437 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,916
Remaining individualsnot grpmax-eligible	0.0021%	47,629
European (non-Finnish)	0.000894%	111,879

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.Ala2953Asp
Coding: c.8858C>A
MANE Select: NM_004006
dbSNP: rs773941387
Type: single nucleotide variant
Location: chrX:31478185 (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.Ala2953Thr 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
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
DMD c.10224-2A>G Likely 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-ala2953asp (accessed [today's date]).

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