Is FLNC p.Val2374= (c.7122C>G) pathogenic?

FLNC p.Val2374= (c.7122C>G) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-28). Very rare (popmax 0.00119%, nfe); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Val2374= (c.7122C>G)?

FLNC p.Val2374= (c.7122C>G) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Val2374= (c.7122C>G) in the general population?

FLNC p.Val2374= (c.7122C>G) is very rare (popmax 0.00119%, nfe) (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Val2374=

c.7122C>G · rs374711133 · VCV1343548

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

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 -7
Overall
CADD	0.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,030 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,613,954 alleles · very rare exomes 14/1,461,754 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00119%	84,288
South Asian	0.0011%	91,086

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.Val2374=
Coding: c.7122C>G
MANE Select: NM_001458
dbSNP: rs374711133
Type: single nucleotide variant
Location: chr7:128854899 (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-val2374 (accessed [today's date]).

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