Is FLNC p.Arg2690= (c.8070G>T) pathogenic?

FLNC p.Arg2690= (c.8070G>T) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0117%, amr); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Arg2690= (c.8070G>T)?

FLNC p.Arg2690= (c.8070G>T) is associated with hypertrophic cardiomyopathy 26, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Arg2690= (c.8070G>T) in the general population?

FLNC p.Arg2690= (c.8070G>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

FLNC p.Arg2690=

c.8070G>T · rs373087529 · VCV290396

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

hypertrophic cardiomyopathy 26

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 0.11	phastCons 0.69
Overall
CADD	4.609	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,940 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00249% 40/1,607,270 alleles · ultra-rare exomes 37/1,455,482 · genomes 3/151,788 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,563
Remaining individualsnot grpmax-eligible	0.00482%	20,741
African / African-American	0.00403%	24,837
European (non-Finnish)	0.0023%	43,499

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.Arg2690=
Coding: c.8070G>T
MANE Select: NM_001458
dbSNP: rs373087529
Type: single nucleotide variant
Location: chr7:128858415 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2690: the 'interaction with inppl1' region; the 'self-association site, tail' region

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

Disease context

hypertrophic cardiomyopathy 26 — 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

Similar variants

FLNC p.Arg2690Gln 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-arg2690 (accessed [today's date]).

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