Is DMD p.Ala525= (c.1575A>G) pathogenic?

DMD p.Ala525= (c.1575A>G) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0786%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala525= (c.1575A>G)?

DMD p.Ala525= (c.1575A>G) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala525= (c.1575A>G) in the general population?

DMD p.Ala525= (c.1575A>G) is ultra-rare (popmax 0.0786%, afr) (gnomAD).

DMD p.Ala525=

c.1575A>G · rs144372300 · VCV518956

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0786%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -3.5, phastCons 0.99
Overall
CADD	7.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0786% African / African-American · 45/57,273 alleles

Filtering AF 0.0603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0539%

Overall 0.00397% 48/1,209,022 alleles · ultra-rare exomes 21/1,096,897 · genomes 27/112,125 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0786%	1,273
Remaining individualsnot grpmax-eligible	0.0042%	23,783
European (non-Finnish)	0.000112%	894,190

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.Ala525=
Coding: c.1575A>G
MANE Select: NM_004006
dbSNP: rs144372300
Type: single nucleotide variant
Location: chrX:32595784 (GRCh38)
Residue 525: a UniProt-annotated variant site (in bmd)

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.Ala525Glu Uncertain significance ★ same residue
DMD p.Ala525Pro Uncertain significance ★ same residue
DMD p.Ala525Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala525 (accessed [today's date]).

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