Is FLNC p.Ala199= (c.597C>T) pathogenic?

FLNC p.Ala199= (c.597C>T) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.11%, mid); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Ala199= (c.597C>T)?

FLNC p.Ala199= (c.597C>T) is associated with hypertrophic cardiomyopathy 26, cardiomyopathy, myofibrillar myopathy 5 (ClinVar).

How common is FLNC p.Ala199= (c.597C>T) in the general population?

FLNC p.Ala199= (c.597C>T) is low-frequency (popmax 1.11%, mid) (gnomAD).

FLNC p.Ala199=

c.597C>T · rs143942649 · VCV195145

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, mid)

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 -0.35	phastCons 0.09
Overall
CADD	8.467	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.11% Middle Eastern · 67/6,062 alleles

Filtering AF 0.893% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.815%

Overall 0.198% 3,199/1,613,138 alleles · low-frequency exomes 3,007/1,460,848 · genomes 192/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.11%	90
Ashkenazi Jewishnot grpmax-eligible	1%	100
Remaining individualsnot grpmax-eligible	0.243%	411
European (non-Finnish)	0.206%	485
South Asian	0.152%	660
Admixed American	0.108%	923
African / African-American	0.0426%	2,345
Finnishnot grpmax-eligible	0.0238%	4,203

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.Ala199=
Coding: c.597C>T
MANE Select: NM_001458
dbSNP: rs143942649
Type: single nucleotide variant
Location: chr7:128835570 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 199: the calponin-homology (ch) 2 domain; the 'actin-binding' region

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.Ala199Thr 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-ala199 (accessed [today's date]).

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