Is FLNC p.Ile2160Phe (c.6478A>T) pathogenic?

FLNC p.Ile2160Phe (c.6478A>T) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-11). AlphaMissense: likely pathogenic (0.8545); Absent from gnomAD v4.1; Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Ile2160Phe (c.6478A>T)?

FLNC p.Ile2160Phe (c.6478A>T) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Ile2160Phe (c.6478A>T) in the general population?

FLNC p.Ile2160Phe (c.6478A>T) is absent from gnomAD v4.1 (gnomAD).

How is Muscle filaminopathy inherited?

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

What do computational predictors say about FLNC p.Ile2160Phe (c.6478A>T)?

AlphaMissense predicts likely pathogenic (score 0.8545) — an in-silico prediction, not a clinical call.

FLNC p.Ile2160Phe

c.6478A>T · rs879255640 · VCV253127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8545 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.8545	likely pathogenic
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNC
Protein: p.Ile2160Phe
Coding: c.6478A>T
MANE Select: NM_001458
dbSNP: rs879255640
Type: single nucleotide variant
Location: chr7:128853831 (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 cardiomyopathy, familial restrictive, 5

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-ile2160phe (accessed [today's date]).

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