Is FLNC p.Arg478= (c.1434C>T) pathogenic?

FLNC p.Arg478= (c.1434C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-03-27). Ultra-rare (popmax 0.0276%, nfe); Associated with cardiomyopathy.

What condition is associated with FLNC p.Arg478= (c.1434C>T)?

FLNC p.Arg478= (c.1434C>T) is associated with cardiomyopathy, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Arg478= (c.1434C>T) in the general population?

FLNC p.Arg478= (c.1434C>T) is ultra-rare (popmax 0.0276%, nfe) (gnomAD).

FLNC p.Arg478=

c.1434C>T · rs201810745 · VCV390849

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, nfe)

Conditions

cardiomyopathy

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 -6.8
Overall
CADD	3.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0276% European (non-Finnish) · 326/1,180,038 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.0224% 362/1,613,930 alleles · ultra-rare exomes 332/1,461,562 · genomes 30/152,368 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0276%	3,620
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.00999%	10,006
African / African-American	0.00799%	12,509
South Asian	0.00768%	13,013
Finnishnot grpmax-eligible	0.00471%	21,245

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.Arg478=
Coding: c.1434C>T
MANE Select: NM_001458
dbSNP: rs201810745
Type: single nucleotide variant
Location: chr7:128840045 (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

cardiomyopathy — 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 hypertrophic cardiomyopathy 26

Similar variants

FLNC p.Arg478His Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNC p.Arg478Pro Uncertain significance ★ ⚠ same residue
FLNC p.Arg478Cys Likely benign ★ 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

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-arg478 (accessed [today's date]).

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