Is FLNC p.Pro764= (c.2292C>T) pathogenic?

FLNC p.Pro764= (c.2292C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-10-01). Rare (popmax 0.101%, mid); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Pro764= (c.2292C>T)?

FLNC p.Pro764= (c.2292C>T) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Pro764= (c.2292C>T) in the general population?

FLNC p.Pro764= (c.2292C>T) is rare (popmax 0.101%, mid) (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Pro764=

c.2292C>T · rs369916201 · VCV258134

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.101%, mid)

Conditions

myofibrillar myopathy 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20
Overall
CADD	0.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% Middle Eastern · 5/4,974 alleles

Filtering AF 0.0395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0257%

Overall 0.00503% 78/1,549,600 alleles · rare exomes 76/1,397,404 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.101%	995
South Asian	0.0167%	6,006
Remaining individualsnot grpmax-eligible	0.01%	9,992
Admixed American	0.00784%	12,752
East Asian	0.00489%	20,464
European (non-Finnish)	0.00384%	26,068
African / African-American	0.00274%	36,511
Finnishnot grpmax-eligible	0.00169%	59,078

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.Pro764=
Coding: c.2292C>T
MANE Select: NM_001458
dbSNP: rs369916201
Type: single nucleotide variant
Location: chr7:128842601 (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: 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.Pro764Arg 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-pro764 (accessed [today's date]).

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