Is FLNC p.Ser566= (c.1698C>T) pathogenic?

FLNC p.Ser566= (c.1698C>T) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-01). Rare (popmax 0.476%, afr); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Ser566= (c.1698C>T)?

FLNC p.Ser566= (c.1698C>T) is associated with hypertrophic cardiomyopathy 26, cardiomyopathy, myofibrillar myopathy 5 (ClinVar).

How common is FLNC p.Ser566= (c.1698C>T) in the general population?

FLNC p.Ser566= (c.1698C>T) is rare (popmax 0.476%, afr) (gnomAD).

FLNC p.Ser566=

c.1698C>T · rs112194548 · VCV193846

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.476%, afr)

Conditions

hypertrophic cardiomyopathy 26

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 5.9	phastCons 1
Overall
CADD	14.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.476% African / African-American · 357/74,948 alleles

Filtering AF 0.436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.42%

Overall 0.0241% 389/1,613,748 alleles · rare exomes 198/1,461,768 · genomes 191/151,980 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.476%	210
Admixed American	0.025%	4,000
Remaining individualsnot grpmax-eligible	0.0224%	4,464
South Asian	0.0011%	91,068
European (non-Finnish)	0.00017%	589,950

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.Ser566=
Coding: c.1698C>T
MANE Select: NM_001458
dbSNP: rs112194548
Type: single nucleotide variant
Location: chr7:128840855 (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

hypertrophic cardiomyopathy 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement

Similar variants

FLNC p.Ser566Cys Uncertain significance ★ 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-ser566 (accessed [today's date]).

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