Is FLNB p.Glu498fs (c.1493del) pathogenic?

FLNB p.Glu498fs (c.1493del) is classified Pathogenic in FLNB (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with spondylocarpotarsal synostosis syndrome.

What condition is associated with FLNB p.Glu498fs (c.1493del)?

FLNB p.Glu498fs (c.1493del) is associated with spondylocarpotarsal synostosis syndrome (ClinVar).

How common is FLNB p.Glu498fs (c.1493del) in the general population?

FLNB p.Glu498fs (c.1493del) is absent from gnomAD (gnomAD).

FLNB p.Glu498fs

c.1493del · rs2107092260 · VCV1332839

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 10 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLNB
Protein: p.Glu498fs
Coding: c.1493del
MANE Select: NM_001457
dbSNP: rs2107092260
Type: Deletion
Location: chr3:58103968 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB

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 c.1346-1358_1941+403del Pathogenic ★ same condition
FLNB c.3127-354_4223-1836del Pathogenic ★ same condition
FLNB c.5555-5_5561del Pathogenic ★ same condition
FLNB p.Gly1149fs Likely pathogenic ★ same condition
FLNB p.Ile1590fs Likely pathogenic ★ same condition
FLNB p.Phe825fs Likely pathogenic ★ same condition
FLNB p.Thr923_Tyr924insTer Likely pathogenic ★ same condition
FLNB p.Tyr1676fs 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/flnb-p-glu498fs (accessed [today's date]).

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