Is FLNC p.Phe2234= (c.6702C>T) pathogenic?

FLNC p.Phe2234= (c.6702C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-13). Ultra-rare (popmax 0.0134%, amr); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Phe2234= (c.6702C>T)?

FLNC p.Phe2234= (c.6702C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Phe2234= (c.6702C>T) in the general population?

FLNC p.Phe2234= (c.6702C>T) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

FLNC p.Phe2234=

c.6702C>T · rs370589662 · VCV472137

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

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
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 -10
Overall
CADD	1.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% Admixed American · 8/59,884 alleles

Filtering AF 0.00663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00124% 20/1,607,730 alleles · ultra-rare exomes 15/1,455,840 · genomes 5/151,890 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,485
African / African-American	0.00802%	12,465
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,450
South Asian	0.0033%	30,301
East Asian	0.00224%	44,732
European (non-Finnish)	8.49e-05%	1,177,485

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.Phe2234=
Coding: c.6702C>T
MANE Select: NM_001458
dbSNP: rs370589662
Type: single nucleotide variant
Location: chr7:128854191 (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-phe2234 (accessed [today's date]).

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