Is FLNC p.Val2015Met (c.6043G>A) pathogenic?

FLNC p.Val2015Met (c.6043G>A) is classified Uncertain significance in FLNC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-09). AlphaMissense: likely pathogenic (0.9563); Very rare (popmax 0.00329%, sas); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Val2015Met (c.6043G>A)?

FLNC p.Val2015Met (c.6043G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Val2015Met (c.6043G>A) in the general population?

FLNC p.Val2015Met (c.6043G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about FLNC p.Val2015Met (c.6043G>A)?

AlphaMissense predicts likely pathogenic (score 0.9563) — an in-silico prediction, not a clinical call.

FLNC p.Val2015Met

c.6043G>A · rs775231810 · VCV658770

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9563 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Cardiovascular phenotype

⚠ 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
AlphaMissense	0.9563	likely pathogenic
REVEL	0.509	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,092 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000372% 6/1,613,748 alleles · very rare exomes 5/1,461,520 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,364
European (non-Finnish)	0.000254%	393,349

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.Val2015Met
Coding: c.6043G>A
MANE Select: NM_001458
dbSNP: rs775231810
Type: single nucleotide variant
Location: chr7:128852866 (GRCh38)

Full FLNC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

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-val2015met (accessed [today's date]).

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