Is FLNC p.Ser2016Ile (c.6047G>T) pathogenic?

FLNC p.Ser2016Ile (c.6047G>T) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). AlphaMissense: likely pathogenic (0.6487); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Ser2016Ile (c.6047G>T)?

FLNC p.Ser2016Ile (c.6047G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is FLNC p.Ser2016Ile (c.6047G>T) in the general population?

FLNC p.Ser2016Ile (c.6047G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNC p.Ser2016Ile (c.6047G>T)?

AlphaMissense predicts likely pathogenic (score 0.6487) — an in-silico prediction, not a clinical call.

FLNC p.Ser2016Ile

c.6047G>T · rs1808881327 · VCV3221744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6487	likely pathogenic
REVEL	0.594	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	26.8	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

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.Ser2016Ile
Coding: c.6047G>T
MANE Select: NM_001458
dbSNP: rs1808881327
Type: single nucleotide variant
Location: chr7:128852870 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2016: the 'required for interaction with pgm5' 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

Similar variants

FLNC p.Ser2016= Conflicting classifications of pathogenicity ★ same residue
FLNC c.1210+1G>A Likely pathogenic ★★ same condition
FLNC c.2550+2T>C Pathogenic/Likely pathogenic ★★ same condition
FLNC c.2930-1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNC c.5199+1G>T Pathogenic/Likely pathogenic ★★ same condition
FLNC c.5398+1G>C Likely pathogenic ★★ same condition
FLNC p.Arg1313Ter Pathogenic/Likely pathogenic ★★ same condition
FLNC p.Arg1341Ter 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-ser2016ile (accessed [today's date]).

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