Is FLNC p.Arg1434= (c.4302C>T) pathogenic?

FLNC p.Arg1434= (c.4302C>T) is classified Benign in FLNC (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.25%, afr); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Arg1434= (c.4302C>T)?

FLNC p.Arg1434= (c.4302C>T) is associated with myofibrillar myopathy 5, cardiomyopathy, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Arg1434= (c.4302C>T) in the general population?

FLNC p.Arg1434= (c.4302C>T) is low-frequency (popmax 3.25%, afr) (gnomAD).

How is Muscle filaminopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FLNC p.Arg1434=

c.4302C>T · rs114697352 · VCV391107

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.25%, afr)

Conditions

myofibrillar myopathy 5

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 0.74	phastCons 1
Overall
CADD	8.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.25% African / African-American · 2,436/75,042 alleles

Filtering AF 3.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.1%

Overall 0.166% 2,687/1,614,060 alleles · low-frequency exomes 1,303/1,461,740 · genomes 1,384/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.25%	31
Remaining individualsnot grpmax-eligible	0.189%	530
Admixed American	0.138%	723
Middle Eastern	0.0661%	1,513
South Asian	0.011%	9,108
East Asian	0.00891%	11,219
European (non-Finnish)	0.00271%	36,874

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.Arg1434=
Coding: c.4302C>T
MANE Select: NM_001458
dbSNP: rs114697352
Type: single nucleotide variant
Location: chr7:128847710 (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

myofibrillar myopathy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

For Muscle filaminopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FLNC p.Arg1434Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNC p.Arg1434His Conflicting classifications of pathogenicity ★ same residue
FLNC p.Arg1434Leu Conflicting classifications of pathogenicity ★ same residue
FLNC p.Arg1434Pro 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

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-arg1434 (accessed [today's date]).

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