Is DMD p.Ala786Asp (c.2357C>A) pathogenic?

DMD p.Ala786Asp (c.2357C>A) is classified Likely benign in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-11). AlphaMissense: likely pathogenic (0.6497); Very rare (popmax 0.00354%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala786Asp (c.2357C>A)?

DMD p.Ala786Asp (c.2357C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is DMD p.Ala786Asp (c.2357C>A) in the general population?

DMD p.Ala786Asp (c.2357C>A) is very rare (popmax 0.00354%, sas) (gnomAD).

What do computational predictors say about DMD p.Ala786Asp (c.2357C>A)?

AlphaMissense predicts likely pathogenic (score 0.6497) — an in-silico prediction, not a clinical call.

DMD p.Ala786Asp

c.2357C>A · VCV4869876

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6497 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00354%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6497	likely pathogenic
REVEL	0.249	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.4	GERP 5.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00354% South Asian · 2/56,473 alleles

Filtering AF 0.000587% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00022%

Overall 0.000166% 2/1,208,377 alleles · very rare exomes 2/1,094,936 · genomes 0/113,441 · 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.Ala786Asp
Coding: c.2357C>A
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32501778 (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

Similar variants

DMD p.Ala786= Likely benign ★ same residue
DMD c.2804-2A>C Pathogenic/Likely pathogenic ★★ same condition
DMD c.31+1G>C Pathogenic ★★ same condition
DMD c.3432+2036A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.3433-1G>A Pathogenic ★★ same condition
DMD c.357+1G>T Pathogenic ★★ same condition
DMD c.9974+1G>A Pathogenic/Likely pathogenic ★★ same condition
DMD p.Arg3034Ter 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-ala786asp (accessed [today's date]).

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