Is DMD p.Ala199Glu (c.596C>A) pathogenic?

DMD p.Ala199Glu (c.596C>A) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-05-25). AlphaMissense: likely pathogenic (0.9874); Absent from gnomAD v4.1; Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Ala199Glu (c.596C>A)?

DMD p.Ala199Glu (c.596C>A) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Ala199Glu (c.596C>A) in the general population?

DMD p.Ala199Glu (c.596C>A) is absent from gnomAD v4.1 (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.Ala199Glu (c.596C>A)?

AlphaMissense predicts likely pathogenic (score 0.9874) — an in-silico prediction, not a clinical call.

DMD p.Ala199Glu

c.596C>A · rs1557047884 · VCV526052

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9874 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9874	likely pathogenic · top 4% in DMD
REVEL	0.949	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala199Glu
Coding: c.596C>A
MANE Select: NM_004006
dbSNP: rs1557047884
Type: single nucleotide variant
Location: chrX:32809546 (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

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.Ala199Pro Uncertain significance ★ ⚠ same residue
DMD p.Ala199= 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

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-ala199glu (accessed [today's date]).

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