Is DMD p.Ala2840= (c.8520A>G) pathogenic?

DMD p.Ala2840= (c.8520A>G) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-10-09). Very rare (popmax 0.00223%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala2840= (c.8520A>G)?

DMD p.Ala2840= (c.8520A>G) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala2840= (c.8520A>G) in the general population?

DMD p.Ala2840= (c.8520A>G) is very rare (popmax 0.00223%, nfe) (gnomAD).

DMD p.Ala2840=

c.8520A>G · rs767304792 · VCV281305

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.004	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3.4
Overall
CADD	2.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% European (non-Finnish) · 20/895,663 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00165% 20/1,212,365 alleles · very rare exomes 20/1,098,201 · genomes 0/114,164 · joint denominator

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.Ala2840=
Coding: c.8520A>G
MANE Select: NM_004006
dbSNP: rs767304792
Type: single nucleotide variant
Location: chrX:31496815 (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.Ala2840Thr 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-ala2840 (accessed [today's date]).

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