Is FLNC p.Ala504= (c.1512C>T) pathogenic?

FLNC p.Ala504= (c.1512C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00119%, nfe); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Ala504= (c.1512C>T)?

FLNC p.Ala504= (c.1512C>T) is associated with hypertrophic cardiomyopathy 26, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Ala504= (c.1512C>T) in the general population?

FLNC p.Ala504= (c.1512C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

FLNC p.Ala504=

c.1512C>T · rs768868050 · VCV1774240

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00119%, 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	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.1
Overall
CADD	7.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,034 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,613,950 alleles · very rare exomes 12/1,461,734 · genomes 2/152,216 · 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.Ala504=
Coding: c.1512C>T
MANE Select: NM_001458
dbSNP: rs768868050
Type: single nucleotide variant
Location: chr7:128840123 (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: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement

Similar variants

FLNC p.Ala504Thr 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-ala504 (accessed [today's date]).

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