Is FLNC p.Val1682fs (c.5044dup) pathogenic?

FLNC p.Val1682fs (c.5044dup) is classified Pathogenic in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). Associated with distal myopathy with posterior leg and anterior hand involvement.

What condition is associated with FLNC p.Val1682fs (c.5044dup)?

FLNC p.Val1682fs (c.5044dup) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

FLNC p.Val1682fs

Q: How is FLNC-related handgrip and calf weakness-distal myopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.5044dup · VCV3750981

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

distal myopathy with posterior leg and anterior hand involvement

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 30 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	phastCons 1

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

Variant & gene context

Gene: FLNC
Protein: p.Val1682fs
Coding: c.5044dup
MANE Select: NM_001458
Type: Duplication
Location: chr7:128849421 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1682: a β-strand

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

Disease context

distal myopathy with posterior leg and anterior hand involvement — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 5 hypertrophic cardiomyopathy 26

For FLNC-related handgrip and calf weakness-distal myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

FLNC p.Val1682Gly Uncertain significance ★★ ⚠ same residue
FLNC p.Val1682Leu Uncertain significance ★ ⚠ same residue
FLNC p.Arg1313fs Pathogenic/Likely pathogenic ★★ same condition
FLNC p.Asn329fs Pathogenic ★★ same condition
FLNC p.Glu365Ter Pathogenic ★★ same condition
FLNC p.Pro611fs Pathogenic/Likely pathogenic ★★ same condition
FLNC p.Thr1684fs Pathogenic ★★ same condition
FLNC p.Tyr1316fs 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/flnc-p-val1682fs (accessed [today's date]).

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