Is DMD p.Gln421Ter (c.1261C>T) pathogenic?

DMD p.Gln421Ter (c.1261C>T) is classified Pathogenic in DMD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-14). Absent from gnomAD v4.1; Associated with neuromuscular disease caused by qualitative or quantitative defects of dystrophin.

How common is DMD p.Gln421Ter (c.1261C>T) in the general population?

DMD p.Gln421Ter (c.1261C>T) is absent from gnomAD v4.1 (gnomAD).

DMD p.Gln421Ter

Q: What condition is associated with DMD p.Gln421Ter (c.1261C>T)?

DMD p.Gln421Ter (c.1261C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dystrophin, Duchenne muscular dystrophy (ClinVar).

c.1261C>T · rs398123852 · VCV94454

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dystrophin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 79
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Gln421Ter
Coding: c.1261C>T
MANE Select: NM_004006
dbSNP: rs398123852
Type: single nucleotide variant
Location: chrX:32644202 (GRCh38)
Residue 421: an α-helix

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

Disease context

neuromuscular disease caused by qualitative or quantitative defects of dystrophin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Gln421Lys Uncertain significance ★ ⚠ same residue
DMD p.Gln421Pro Uncertain significance ★ ⚠ same residue
DMD p.Gln421= Likely benign ★ same residue
DMD p.Gln421Glu Likely benign ★ same residue
DMD p.Gln421fs Pathogenic ★ 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

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-gln421ter (accessed [today's date]).

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