Is DMD p.Ala27Val (c.80C>T) pathogenic?

DMD p.Ala27Val (c.80C>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.2601); Ultra-rare (popmax 0.0123%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala27Val (c.80C>T)?

DMD p.Ala27Val (c.80C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala27Val (c.80C>T) in the general population?

DMD p.Ala27Val (c.80C>T) is ultra-rare (popmax 0.0123%, afr) (gnomAD).

What do computational predictors say about DMD p.Ala27Val (c.80C>T)?

AlphaMissense predicts likely benign (score 0.2601) — an in-silico prediction, not a clinical call.

DMD p.Ala27Val

c.80C>T · rs763407275 · VCV1004607

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2601 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2601	likely benign
REVEL	0.481	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	23.3	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 0.0123% African / African-American · 7/56,749 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00408%

Overall 0.000758% 9/1,188,099 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0123%	8,107
Admixed American	0.00223%	44,862
Remaining individualsnot grpmax-eligible	0.00214%	46,772

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.Ala27Val
Coding: c.80C>T
MANE Select: NM_004006
dbSNP: rs763407275
Type: single nucleotide variant
Location: chrX:33020152 (GRCh38)
Residue 27: the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region

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.Ala27Glu Uncertain significance ★★ ⚠ same residue
DMD p.Ala27Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Ala27= Likely benign ★ 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

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-ala27val (accessed [today's date]).

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