Is DMD p.Ile749= (c.2247C>A) pathogenic?

DMD p.Ile749= (c.2247C>A) is classified Likely benign in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). Very rare (popmax 0.00875%, afr); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Ile749= (c.2247C>A)?

DMD p.Ile749= (c.2247C>A) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Ile749= (c.2247C>A) in the general population?

DMD p.Ile749= (c.2247C>A) is very rare (popmax 0.00875%, afr) (gnomAD).

How is Duchenne muscular dystrophy inherited?

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

DMD p.Ile749=

c.2247C>A · rs745778664 · VCV1476201

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00875%, afr)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 4.7, phastCons 1
Overall
CADD	8.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00875% African / African-American · 5/57,126 alleles

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

Overall 0.000579% 7/1,208,215 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00875%	11,425
East Asian	0.00296%	33,749
Remaining individualsnot grpmax-eligible	0.0021%	47,549

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.Ile749=
Coding: c.2247C>A
MANE Select: NM_004006
dbSNP: rs745778664
Type: single nucleotide variant
Location: chrX:32518053 (GRCh38)

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

For Duchenne muscular dystrophy (Orphanet):

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

Similar variants

DMD p.Ile749Val Conflicting classifications of pathogenicity ★ ⚠ 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-ile749 (accessed [today's date]).

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