Is DMD p.Leu352Phe (c.1056A>T) pathogenic?

DMD p.Leu352Phe (c.1056A>T) is classified Uncertain significance in DMD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely pathogenic (0.7246); Absent from gnomAD v4.1; Associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency.

How common is DMD p.Leu352Phe (c.1056A>T) in the general population?

DMD p.Leu352Phe (c.1056A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Leu352Phe (c.1056A>T)?

AlphaMissense predicts likely pathogenic (score 0.7246) — an in-silico prediction, not a clinical call.

DMD p.Leu352Phe

Q: What condition is associated with DMD p.Leu352Phe (c.1056A>T)?

DMD p.Leu352Phe (c.1056A>T) is associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency (ClinVar).

c.1056A>T · VCV4066547

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7246 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.7246	likely pathogenic
REVEL	0.504	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.34	GERP -4.5, phastCons 0.016
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	16.53	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

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.Leu352Phe
Coding: c.1056A>T
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32645057 (GRCh38)
Residue 352: an α-helix

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.Leu352= Likely benign ★ 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
DMD c.1705-2A>G 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-leu352phe (accessed [today's date]).

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