Is DYSF p.Asp336Ile (c.1006_1007delinsAT) pathogenic?

DYSF p.Asp336Ile (c.10061007delinsAT) is classified Uncertain significance in DYSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-17). Absent from gnomAD; Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

What condition is associated with DYSF p.Asp336Ile (c.1006_1007delinsAT)?

DYSF p.Asp336Ile (c.1006_1007delinsAT) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Asp336Ile (c.1006_1007delinsAT) in the general population?

DYSF p.Asp336Ile (c.1006_1007delinsAT) is absent from gnomAD (gnomAD).

DYSF p.Asp336Ile

c.1006_1007delinsAT · rs886043469 · VCV286744

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DYSF
Protein: p.Asp336Ile
Coding: c.1006_1007delinsAT
MANE Select: NM_001130987
dbSNP: rs886043469
Type: Indel
Location: chr2:71520181 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 336: a β-strand

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.Asp336= Conflicting classifications of pathogenicity ★ same residue
DYSF p.Asp336Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
DYSF p.Tyr1166_Gly1167delinsTer Pathogenic ★★★ same condition
DYSF p.Glu453Gln Uncertain significance ★★ same condition
DYSF c.1150-43_1155delinsA Likely pathogenic ★ same condition
DYSF p.Cys1006_Pro1007delinsTer Pathogenic ★ same condition
DYSF p.Leu734fs Pathogenic ★ same condition
DYSF p.Val1127fs 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-asp336ile (accessed [today's date]).

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