Is FLNC p.Ser2598= (c.7794C>T) pathogenic?

FLNC p.Ser2598= (c.7794C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-12). Very rare (popmax 0.00694%, eas); Associated with distal myopathy with posterior leg and anterior hand involvement.

What condition is associated with FLNC p.Ser2598= (c.7794C>T)?

FLNC p.Ser2598= (c.7794C>T) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Ser2598= (c.7794C>T) in the general population?

FLNC p.Ser2598= (c.7794C>T) is very rare (popmax 0.00694%, eas) (gnomAD).

FLNC p.Ser2598=

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.7794C>T · rs1013763254 · VCV762681

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00694%, eas)

Conditions

distal myopathy with posterior leg and anterior hand involvement

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.2	phastCons 0.001
Overall
CADD	8.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00694% East Asian · 3/43,200 alleles

Filtering AF 0.00184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00091%

Overall 0.000586% 9/1,535,700 alleles · very rare exomes 6/1,383,552 · genomes 3/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00694%	14,400
Remaining individualsnot grpmax-eligible	0.00168%	59,670
South Asian	0.00117%	85,586
European (non-Finnish)	0.000357%	280,203

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.Ser2598=
Coding: c.7794C>T
MANE Select: NM_001458
dbSNP: rs1013763254
Type: single nucleotide variant
Location: chr7:128858021 (GRCh38)

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

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-ser2598 (accessed [today's date]).

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