Is DMD p.Ala27Pro (c.79G>C) pathogenic?

DMD p.Ala27Pro (c.79G>C) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.9797); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala27Pro (c.79G>C)?

DMD p.Ala27Pro (c.79G>C) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Ala27Pro (c.79G>C) in the general population?

DMD p.Ala27Pro (c.79G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Ala27Pro (c.79G>C)?

AlphaMissense predicts likely pathogenic (score 0.9797) — an in-silico prediction, not a clinical call.

DMD p.Ala27Pro

c.79G>C · rs886043234 · VCV285850

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9797 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9797	likely pathogenic · top 6% in DMD
REVEL	0.744	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMD
Protein: p.Ala27Pro
Coding: c.79G>C
MANE Select: NM_004006
dbSNP: rs886043234
Type: single nucleotide variant
Location: chrX:33020153 (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: Duchenne muscular dystrophy

Similar variants

DMD p.Ala27Glu Uncertain significance ★★ ⚠ same residue
DMD p.Ala27Val Uncertain significance ★★ 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-ala27pro (accessed [today's date]).

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