Is DMD p.Ala1235= (c.3705C>T) pathogenic?

DMD p.Ala1235= (c.3705C>T) is classified Benign in DMD (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-03). Common (popmax 5.02%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala1235= (c.3705C>T)?

DMD p.Ala1235= (c.3705C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

DMD p.Ala1235=

Q: How common is DMD p.Ala1235= (c.3705C>T) in the general population?

DMD p.Ala1235= (c.3705C>T) is common (popmax 5.02%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3705C>T · rs143628111 · VCV94603

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 5.02%, afr) — too common for a highly-penetrant pathogenic allele

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 3.9	GERP 0.64, phastCons 1
Overall
CADD	8.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.02% African / African-American · 2,860/56,918 alleles

Filtering AF 4.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.81%

Overall 0.265% 3,196/1,206,657 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.02%	20
Admixed American	0.344%	290
Remaining individualsnot grpmax-eligible	0.308%	325
Middle Eastern	0.161%	619
South Asian	0.00352%	28,397
European (non-Finnish)	0.00269%	37,200

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.Ala1235=
Coding: c.3705C>T
MANE Select: NM_004006
dbSNP: rs143628111
Type: single nucleotide variant
Location: chrX:32448537 (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 dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

DMD p.Ala1235Val 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-ala1235 (accessed [today's date]).

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