Is FLNC p.Ser868fs (c.2604del) pathogenic?

FLNC p.Ser868fs (c.2604del) is classified Pathogenic in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-25). No gnomAD frequency available for this variant; Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Ser868fs (c.2604del)?

FLNC p.Ser868fs (c.2604del) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Ser868fs (c.2604del) in the general population?

FLNC p.Ser868fs (c.2604del) is no gnomAD frequency available for this variant (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Ser868fs

c.2604del · rs2128935921 · VCV1069877

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

myofibrillar myopathy 5

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 17 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	phastCons 1

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

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: FLNC
Protein: p.Ser868fs
Coding: c.2604del
MANE Select: NM_001458
dbSNP: rs2128935921
Type: Deletion
Location: chr7:128843282 (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

myofibrillar myopathy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

For Muscle filaminopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FLNC p.Ser868Arg Uncertain significance ★★ same residue
FLNC p.Ser868Gly Conflicting classifications of pathogenicity ★ same residue
FLNC p.Ser868= Likely benign ★ same residue
FLNC c.2390-10_2406del Pathogenic ★★ same condition
FLNC c.2929+2_2929+7del Likely pathogenic ★★ same condition
FLNC p.Ala1902fs Pathogenic ★★ same condition
FLNC p.Ala260fs Pathogenic ★★ same condition
FLNC p.Ala656fs 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/flnc-p-ser868fs (accessed [today's date]).

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