Is DMD p.Ala199= (c.597A>G) pathogenic?

DMD p.Ala199= (c.597A>G) is classified Uncertain significance in DMD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-27). Absent from gnomAD v4.1; Associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency.

How common is DMD p.Ala199= (c.597A>G) in the general population?

DMD p.Ala199= (c.597A>G) is absent from gnomAD v4.1 (gnomAD).

DMD p.Ala199=

Q: What condition is associated with DMD p.Ala199= (c.597A>G)?

DMD p.Ala199= (c.597A>G) is associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency (ClinVar).

c.597A>G · VCV4065960

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency

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 0.43	GERP -3.5, phastCons 1
Overall
CADD	10.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMD
Protein: p.Ala199=
Coding: c.597A>G
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32809545 (GRCh38)
Residue 199: an α-helix; the calponin-homology (ch) 2 domain; the 'actin-binding' region

Full DMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency

Similar variants

DMD p.Ala199Glu Uncertain significance ★★ ⚠ same residue
DMD p.Ala199Pro Uncertain significance ★ ⚠ same residue
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10224-2A>G Likely pathogenic ★★ same condition
DMD c.10797+1G>A Pathogenic ★★ same condition
DMD c.1150-1G>A Pathogenic ★★ same condition
DMD c.1483-1G>A Likely pathogenic ★★ same condition
DMD c.1603-2A>C Pathogenic/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-ala199 (accessed [today's date]).

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