Is FLNC p.Leu50Phe (c.147_148delinsTT) pathogenic?

FLNC p.Leu50Phe (c.147148delinsTT) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-19). Associated with distal myopathy with posterior leg and anterior hand involvement.

FLNC p.Leu50Phe

Q: What condition is associated with FLNC p.Leu50Phe (c.147_148delinsTT)?

FLNC p.Leu50Phe (c.147_148delinsTT) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

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.147_148delinsTT · VCV3760114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.17	phastCons 0.96
Regional constraint	o/e 0.34	constrained · MANE · 84 bp · p 5.6e-05 · regional, not allelic

Variant & gene context

Gene: FLNC
Protein: p.Leu50Phe
Coding: c.147_148delinsTT
MANE Select: NM_001458
Type: Indel
Location: chr7:128830784 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 50: the calponin-homology (ch) 1 domain; the 'actin-binding' region

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.Leu50fs Pathogenic ★ same residue
FLNC p.Leu50Val Uncertain significance ★ ⚠ same residue
FLNC p.Leu50= Benign ★ same residue
FLNC p.Asp1086Val Uncertain significance ★★ same condition
FLNC p.Ser101Asn Uncertain significance ★★ same condition
FLNC c.2920_2929+6delinsTCCA Likely pathogenic ★ same condition
FLNC c.2920_2929+6delinsTCCCA Likely pathogenic ★ same condition
FLNC p.Ala1183Leu 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-leu50phe (accessed [today's date]).

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