Is FLNC p.Val2267= (c.6801C>T) pathogenic?

FLNC p.Val2267= (c.6801C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Very rare (popmax 0.00534%, afr); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Val2267= (c.6801C>T)?

FLNC p.Val2267= (c.6801C>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.Val2267= (c.6801C>T) in the general population?

FLNC p.Val2267= (c.6801C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Val2267=

c.6801C>T · rs768689551 · VCV742627

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

myofibrillar myopathy 5

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.6
Overall
CADD	0.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,882 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000809% 13/1,606,630 alleles · very rare exomes 9/1,454,354 · genomes 4/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,720
Admixed American	0.0017%	58,792
Finnishnot grpmax-eligible	0.00159%	63,020
European (non-Finnish)	0.000595%	168,162

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.Val2267=
Coding: c.6801C>T
MANE Select: NM_001458
dbSNP: rs768689551
Type: single nucleotide variant
Location: chr7:128854486 (GRCh38)

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

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-val2267 (accessed [today's date]).

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