Is DMD p.Asp2837Asn (c.8509G>A) pathogenic?

DMD p.Asp2837Asn (c.8509G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-20). AlphaMissense: ambiguous (0.3567); Ultra-rare (popmax 0.0178%, eas); Associated with dilated cardiomyopathy 3B.

What condition is associated with DMD p.Asp2837Asn (c.8509G>A)?

DMD p.Asp2837Asn (c.8509G>A) is associated with dilated cardiomyopathy 3B, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Asp2837Asn (c.8509G>A) in the general population?

DMD p.Asp2837Asn (c.8509G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DMD p.Asp2837Asn (c.8509G>A)?

AlphaMissense predicts ambiguous (score 0.3567) — an in-silico prediction, not a clinical call.

DMD p.Asp2837Asn

c.8509G>A · rs965718917 · VCV368236

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.3567 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

dilated cardiomyopathy 3B

Computational evidence

Protein change
AlphaMissense	0.3567	ambiguous
REVEL	0.438	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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	26.0	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 0.0178% East Asian · 6/33,784 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00527%

Overall 0.00206% 25/1,210,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,631
Remaining individualsnot grpmax-eligible	0.0042%	23,805
Admixed American	0.00218%	45,867
European (non-Finnish)	0.00179%	55,965

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.Asp2837Asn
Coding: c.8509G>A
MANE Select: NM_004006
dbSNP: rs965718917
Type: single nucleotide variant
Location: chrX:31496826 (GRCh38)

Full DMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Asp2837= 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
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-asp2837asn (accessed [today's date]).

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