Is FLNC p.Phe2649= (c.7947C>T) pathogenic?

FLNC p.Phe2649= (c.7947C>T) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-01). Rare (popmax 0.133%, nfe); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Phe2649= (c.7947C>T)?

FLNC p.Phe2649= (c.7947C>T) is associated with hypertrophic cardiomyopathy 26, cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is FLNC p.Phe2649= (c.7947C>T) in the general population?

FLNC p.Phe2649= (c.7947C>T) is rare (popmax 0.133%, nfe) (gnomAD).

FLNC p.Phe2649=

c.7947C>T · rs368849358 · VCV258153

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.133%, nfe)

Conditions

hypertrophic cardiomyopathy 26

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1
Overall
CADD	7.197	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.133% European (non-Finnish) · 1,510/1,135,688 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.105% 1,645/1,564,578 alleles · rare exomes 1,522/1,412,364 · genomes 123/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.133%	752
Remaining individualsnot grpmax-eligible	0.0987%	1,014
South Asian	0.0367%	2,722
Middle Eastern	0.0339%	2,949
Admixed American	0.0334%	2,994
African / African-American	0.0215%	4,644
Finnishnot grpmax-eligible	0.00631%	15,853

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.Phe2649=
Coding: c.7947C>T
MANE Select: NM_001458
dbSNP: rs368849358
Type: single nucleotide variant
Location: chr7:128858174 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2649: the 'interaction with inppl1' region; the 'self-association site, tail' 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 dilated cardiomyopathy hypertrophic cardiomyopathy myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement

Similar variants

FLNC p.Phe2649Ser 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-phe2649 (accessed [today's date]).

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