Is FLNB p.Cys1095fs (c.3282_3283insAGCA) pathogenic?

FLNB p.Cys1095fs (c.32823283insAGCA) is classified Likely pathogenic in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). Associated with spondylocarpotarsal synostosis syndrome.

What condition is associated with FLNB p.Cys1095fs (c.3282_3283insAGCA)?

FLNB p.Cys1095fs (c.3282_3283insAGCA) is associated with spondylocarpotarsal synostosis syndrome (ClinVar).

FLNB p.Cys1095fs

c.3282_3283insAGCA · VCV3366935

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spondylocarpotarsal synostosis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.2	GERP -0.3, phastCons 0.25

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: FLNB
Protein: p.Cys1095fs
Coding: c.3282_3283insAGCA
MANE Select: NM_001457
Type: Insertion
Location: chr3:58123248 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1095: a β-strand

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

Disease context

spondylocarpotarsal synostosis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Arg1948Ter Pathogenic ★★ same condition
FLNB p.Arg649Ter Pathogenic ★★ same condition
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB p.His532fs Pathogenic/Likely pathogenic ★★ same condition
FLNB c.3724+4G>C Uncertain significance ★★ same condition
FLNB p.Arg1545Gln Uncertain significance ★★ ⚠ same condition
FLNB p.Arg2289His Uncertain significance ★★ ⚠ 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/flnb-p-cys1095fs (accessed [today's date]).

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