Is DMD p.Gln133His (c.399A>T) pathogenic?

DMD p.Gln133His (c.399A>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.855); Very rare (popmax 0.00175%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Gln133His (c.399A>T)?

DMD p.Gln133His (c.399A>T) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Gln133His (c.399A>T) in the general population?

DMD p.Gln133His (c.399A>T) is very rare (popmax 0.00175%, afr) (gnomAD).

What do computational predictors say about DMD p.Gln133His (c.399A>T)?

AlphaMissense predicts likely pathogenic (score 0.855) — an in-silico prediction, not a clinical call.

DMD p.Gln133His

c.399A>T · rs1358899513 · VCV1002679

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.855 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.855	likely pathogenic
REVEL	0.741	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 5	GERP -2.5, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.00175% African / African-American · 1/57,236 alleles

Overall 0.000893% 1/111,949 alleles · very rare

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.Gln133His
Coding: c.399A>T
MANE Select: NM_004006
dbSNP: rs1358899513
Type: single nucleotide variant
Location: chrX:32816599 (GRCh38)
Residue 133: the 'actin-binding' region; a UniProt-annotated variant site (in)

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: Duchenne muscular dystrophy

Similar variants

DMD p.Gln133Ter Pathogenic ★★ same residue
DMD p.Gln133Glu 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-gln133his (accessed [today's date]).

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