Is FLNC p.Ala2408= (c.7224T>G) pathogenic?

FLNC p.Ala2408= (c.7224T>G) is classified Likely benign in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-20). Very rare (popmax 8.48e-05%, nfe); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Ala2408= (c.7224T>G)?

FLNC p.Ala2408= (c.7224T>G) is associated with hypertrophic cardiomyopathy 26, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Ala2408= (c.7224T>G) in the general population?

FLNC p.Ala2408= (c.7224T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

FLNC p.Ala2408=

c.7224T>G · rs2128939770 · VCV1538219

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 -3.8
Overall
CADD	6.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,336 alleles

Overall 6.2e-05% 1/1,613,106 alleles · very rare exomes 1/1,460,890 · genomes 0/152,216 · joint denominator

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.Ala2408=
Coding: c.7224T>G
MANE Select: NM_001458
dbSNP: rs2128939770
Type: single nucleotide variant
Location: chr7:128855287 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2408: an α-helix; the 'interaction with inppl1' 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: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement

Similar variants

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
FLNC c.2930-1G>A 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-ala2408 (accessed [today's date]).

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