Is DMD p.Val83Ile (c.247G>A) pathogenic?

DMD p.Val83Ile (c.247G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0928); Very rare (popmax 0.00875%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Val83Ile (c.247G>A)?

DMD p.Val83Ile (c.247G>A) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Val83Ile (c.247G>A) in the general population?

DMD p.Val83Ile (c.247G>A) is very rare (popmax 0.00875%, afr) (gnomAD).

What do computational predictors say about DMD p.Val83Ile (c.247G>A)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

DMD p.Val83Ile

c.247G>A · rs1358774744 · VCV515175

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00875%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.303	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 0.35, phastCons 0.52
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	10.15	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 0.00875% African / African-American · 5/57,145 alleles

Filtering AF 0.00339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.000662% 8/1,209,258 alleles · very rare exomes 7/1,097,191 · genomes 1/112,067 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00875%	11,429
South Asian	0.00528%	18,946

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.Val83Ile
Coding: c.247G>A
MANE Select: NM_004006
dbSNP: rs1358774744
Type: single nucleotide variant
Location: chrX:32844800 (GRCh38)
Residue 83: the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region

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.Val83Phe Uncertain significance ★ same residue
DMD p.Val83fs Likely pathogenic ★ 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

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-val83ile (accessed [today's date]).

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