Is FLNC p.Ile2707= (c.8121T>C) pathogenic?

FLNC p.Ile2707= (c.8121T>C) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.86%, afr); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Ile2707= (c.8121T>C)?

FLNC p.Ile2707= (c.8121T>C) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Ile2707= (c.8121T>C) in the general population?

FLNC p.Ile2707= (c.8121T>C) is low-frequency (popmax 3.86%, afr) (gnomAD).

FLNC p.Ile2707=

c.8121T>C · rs28437296 · VCV129101

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.86%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11
Overall
CADD	0.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.86% African / African-American · 2,842/73,548 alleles

Filtering AF 3.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.7%

Overall 0.431% 6,937/1,608,118 alleles · low-frequency exomes 4,541/1,456,146 · genomes 2,396/151,972 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.86%	26
South Asian	2.14%	47
East Asian	1.64%	61
Remaining individualsnot grpmax-eligible	0.465%	215
Admixed American	0.302%	331
Middle Eastern	0.25%	400
European (non-Finnish)	0.0807%	1,240
Finnishnot grpmax-eligible	0.0172%	5,819
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Ile2707=
Coding: c.8121T>C
MANE Select: NM_001458
dbSNP: rs28437296
Type: single nucleotide variant
Location: chr7:128858466 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2707: a β-strand; 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

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

Similar variants

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
FLNC c.2930-1G>A 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-ile2707 (accessed [today's date]).

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