Is FLNC p.Arg575= (c.1723C>A) pathogenic?

FLNC p.Arg575= (c.1723C>A) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). Absent from gnomAD v4.1; Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Arg575= (c.1723C>A)?

FLNC p.Arg575= (c.1723C>A) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Arg575= (c.1723C>A) in the general population?

FLNC p.Arg575= (c.1723C>A) is absent from gnomAD v4.1 (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Arg575=

c.1723C>A · rs761117952 · VCV2033965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

myofibrillar myopathy 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor loss, 46 bp away · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Overall
CADD	11.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNC
Protein: p.Arg575=
Coding: c.1723C>A
MANE Select: NM_001458
dbSNP: rs761117952
Type: single nucleotide variant
Location: chr7:128840880 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 575: a β-strand

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: 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.Arg575Gln Uncertain significance ★★ ⚠ same residue
FLNC p.Arg575Trp Uncertain significance ★★ ⚠ same residue
FLNC p.Arg575Pro 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

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-arg575 (accessed [today's date]).

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