Is FLNC p.Ser1624= (c.4872G>A) pathogenic?

FLNC p.Ser1624= (c.4872G>A) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). Ultra-rare (popmax 0.0307%, sas); Associated with distal myopathy with posterior leg and anterior hand involvement.

What condition is associated with FLNC p.Ser1624= (c.4872G>A)?

FLNC p.Ser1624= (c.4872G>A) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Ser1624= (c.4872G>A) in the general population?

FLNC p.Ser1624= (c.4872G>A) is ultra-rare (popmax 0.0307%, sas) (gnomAD).

FLNC p.Ser1624=

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.4872G>A · rs767264014 · VCV539500

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -20
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% South Asian · 28/91,084 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00273% 44/1,613,456 alleles · ultra-rare exomes 40/1,461,428 · genomes 4/152,028 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0307%	3,253
African / African-American	0.00668%	14,977
Remaining individualsnot grpmax-eligible	0.0032%	31,241
Admixed American	0.00167%	59,990
European (non-Finnish)	0.000678%	147,496

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.Ser1624=
Coding: c.4872G>A
MANE Select: NM_001458
dbSNP: rs767264014
Type: single nucleotide variant
Location: chr7:128848927 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1624: a UniProt-annotated variant site (in rcm5; increased protein aggregates; effect on cytoplasm localization; localized in perinuclear region of cytoplasm; no effect on expression)

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.Ser1624Leu Pathogenic/Likely pathogenic ★★ same residue
FLNC c.1047+1G>T Likely pathogenic ★★ same condition
FLNC c.1048-1G>A Likely pathogenic ★★ same condition
FLNC c.1210+1G>A Likely pathogenic ★★ same condition
FLNC c.1549+2T>G Likely pathogenic ★★ same condition
FLNC c.2007+1G>A Likely pathogenic ★★ same condition
FLNC c.2550+1G>C Likely pathogenic ★★ same condition
FLNC c.2550+2T>C 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-ser1624 (accessed [today's date]).

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