Is FLNC p.Arg629fs (c.1861_1885dup) pathogenic?

FLNC p.Arg629fs (c.18611885dup) is classified Pathogenic in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-06). Very rare (popmax 0.000169%, nfe); Associated with distal myopathy with posterior leg and anterior hand involvement.

How common is FLNC p.Arg629fs (c.1861_1885dup) in the general population?

FLNC p.Arg629fs (c.1861_1885dup) is very rare (popmax 0.000169%, nfe) (gnomAD).

FLNC p.Arg629fs

Q: What condition is associated with FLNC p.Arg629fs (c.1861_1885dup)?

FLNC p.Arg629fs (c.1861_1885dup) 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.1861_1885dup · rs1585156327 · VCV663736

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 12 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,972 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,018 alleles · very rare exomes 2/1,461,820 · genomes 0/152,198 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FLNC
Protein: p.Arg629fs
Coding: c.1861_1885dup
MANE Select: NM_001458
dbSNP: rs1585156327
Type: Duplication
Location: chr7:128841215 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 629: 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.Arg629Gln Conflicting classifications of pathogenicity ★ same residue
FLNC p.Arg629Trp Conflicting classifications of pathogenicity ★ same residue
FLNC p.Arg629= Likely benign ★ 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

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-arg629fs (accessed [today's date]).

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