Is DMD p.Gln1448Ter (c.4342C>T) pathogenic?

DMD p.Gln1448Ter (c.4342C>T) is classified Likely pathogenic in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-07). Very rare (popmax 0.000113%, nfe); Associated with progressive muscular dystrophy.

What condition is associated with DMD p.Gln1448Ter (c.4342C>T)?

DMD p.Gln1448Ter (c.4342C>T) is associated with progressive muscular dystrophy (ClinVar).

How common is DMD p.Gln1448Ter (c.4342C>T) in the general population?

DMD p.Gln1448Ter (c.4342C>T) is very rare (popmax 0.000113%, nfe) (gnomAD).

DMD p.Gln1448Ter

c.4342C>T · rs2097990454 · VCV983946

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Conditions

progressive muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 31 of 79
Splicing
SpliceAI	Δ0.52	donor loss · deltas
Pangolin	Δ0.42	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.8	GERP 2.8, phastCons 1
Overall
CADD	48.0	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

Grpmax group 0.000113% European (non-Finnish) · 1/884,743 alleles

Overall 9.21e-05% 1/1,086,186 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.Gln1448Ter
Coding: c.4342C>T
MANE Select: NM_004006
dbSNP: rs2097990454
Type: single nucleotide variant
Location: chrX:32390073 (GRCh38)
Residue 1448: the 'interaction with synm' region

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

Disease context

progressive muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DMD p.Gln1448Leu Uncertain significance ★ ⚠ same residue
DMD c.2168+2T>C Pathogenic/Likely pathogenic ★★ same condition
DMD c.960+1G>A Likely pathogenic ★★ same condition
DMD p.Arg768Ter Pathogenic ★★ same condition
DMD p.Gln1054Ter Pathogenic/Likely pathogenic ★★ same condition
DMD p.Gln1932Ter Pathogenic/Likely pathogenic ★★ same condition
DMD p.Glu1795Ter Pathogenic/Likely pathogenic ★★ same condition
DMD p.Glu3032Ter 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-gln1448ter (accessed [today's date]).

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