Is FLNC p.Ser339fs (c.1015_1016del) pathogenic?

FLNC p.Ser339fs (c.10151016del) is classified Pathogenic in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Ser339fs (c.1015_1016del)?

FLNC p.Ser339fs (c.1015_1016del) is associated with hypertrophic cardiomyopathy 26, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

FLNC p.Ser339fs

c.1015_1016del · VCV4812554

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hypertrophic cardiomyopathy 26

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 6 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.7	phastCons 1

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

Variant & gene context

Gene: FLNC
Protein: p.Ser339fs
Coding: c.1015_1016del
MANE Select: NM_001458
Type: Microsatellite
Location: chr7:128838030 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

hypertrophic cardiomyopathy 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement

Similar variants

FLNC p.Val2614fs Pathogenic/Likely pathogenic ★★ same condition
FLNC p.Asn1909del Uncertain significance ★★ same condition
FLNC p.Pro1757del Uncertain significance ★★ same condition
FLNC p.Ser2633del Uncertain significance ★★ same condition
FLNC c.4289-7_4289-5del Likely benign ★★ same condition
FLNC c.4737+9_4737+10del Benign ★★ same condition
FLNC p.Gln1956fs Likely pathogenic ★ same condition
FLNC p.Thr1317fs 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-ser339fs (accessed [today's date]).

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