Is DMD p.Val100Ile (c.298G>A) pathogenic?

DMD p.Val100Ile (c.298G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.2275); Very rare (popmax 0.00269%, nfe); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Val100Ile (c.298G>A)?

DMD p.Val100Ile (c.298G>A) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Val100Ile (c.298G>A) in the general population?

DMD p.Val100Ile (c.298G>A) is very rare (popmax 0.00269%, nfe) (gnomAD).

How is Duchenne muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMD p.Val100Ile (c.298G>A)?

AlphaMissense predicts likely benign (score 0.2275) — an in-silico prediction, not a clinical call.

DMD p.Val100Ile

c.298G>A · rs779099343 · VCV228583

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2275 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2275	likely benign
REVEL	0.692	pathogenic-leaning
SaProt	—	not scored · why
⇒ REVEL calls this damaging; AlphaMissense 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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	25.6	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 0.00269% European (non-Finnish) · 24/892,320 alleles

Filtering AF 0.00182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00153%

Overall 0.00207% 25/1,206,156 alleles · very rare exomes 23/1,094,839 · genomes 2/111,317 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00269%	37,180
South Asian	0.00176%	56,687

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.Val100Ile
Coding: c.298G>A
MANE Select: NM_004006
dbSNP: rs779099343
Type: single nucleotide variant
Location: chrX:32823354 (GRCh38)
Residue 100: 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

Duchenne muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy Becker muscular dystrophy dilated cardiomyopathy 3B

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Val100Leu 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-val100ile (accessed [today's date]).

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