Is DMD p.Ile749Val (c.2245A>G) pathogenic?

DMD p.Ile749Val (c.2245A>G) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-11-16). AlphaMissense: likely benign (0.058); Ultra-rare (popmax 0.0122%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ile749Val (c.2245A>G)?

DMD p.Ile749Val (c.2245A>G) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is DMD p.Ile749Val (c.2245A>G) in the general population?

DMD p.Ile749Val (c.2245A>G) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about DMD p.Ile749Val (c.2245A>G)?

AlphaMissense predicts likely benign (score 0.058) — an in-silico prediction, not a clinical call.

DMD p.Ile749Val

c.2245A>G · rs771803281 · VCV226049

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.058 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.058	likely benign
REVEL	0.058	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.043	GERP -2.3, phastCons 0.48
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	4.115	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 0.0122% European (non-Finnish) · 109/894,022 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0096%

Overall 0.00927% 112/1,208,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0122%	8,202
Remaining individualsnot grpmax-eligible	0.00421%	23,777
African / African-American	0.00175%	57,161

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.Ile749Val
Coding: c.2245A>G
MANE Select: NM_004006
dbSNP: rs771803281
Type: single nucleotide variant
Location: chrX:32518055 (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 dilated cardiomyopathy Becker muscular dystrophy dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

DMD p.Ile749= 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-ile749val (accessed [today's date]).

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