Is DYSF p.Pro424fs (c.1271del) pathogenic?

DYSF p.Pro424fs (c.1271del) is classified Pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-04). Very rare (popmax 8.49e-05%, nfe); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Pro424fs (c.1271del) in the general population?

DYSF p.Pro424fs (c.1271del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

DYSF p.Pro424fs

Q: What condition is associated with DYSF p.Pro424fs (c.1271del)?

DYSF p.Pro424fs (c.1271del) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.1271del · rs2152748702 · VCV1069450

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.27	GERP -4.2, phastCons 0.009

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,246 alleles

Overall 6.86e-05% 1/1,458,370 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: DYSF
Protein: p.Pro424fs
Coding: c.1271del
MANE Select: NM_001130987
dbSNP: rs2152748702
Type: Deletion
Location: chr2:71526340 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 424: a β-strand; the c2 3 domain

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

Disease context

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

Similar variants

DYSF p.Pro424Leu Uncertain significance ★★ ⚠ same residue
DYSF p.Pro424Thr Uncertain significance ★ ⚠ same residue
DYSF p.Pro424= Likely benign ★ same residue
DYSF c.951+1del Pathogenic ★★★ same condition
DYSF p.Ala927Leufs Pathogenic ★★★ same condition
DYSF p.Asp1181fs Pathogenic ★★★ same condition
DYSF p.Asp1255fs Pathogenic ★★★ same condition
DYSF p.Gln1985fs 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/dysf-p-pro424fs (accessed [today's date]).

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