Is FLNB p.Phe825fs (c.2474_2475del) pathogenic?

FLNB p.Phe825fs (c.24742475del) is classified Likely pathogenic in FLNB (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.0011%, sas); Associated with spondylocarpotarsal synostosis syndrome.

What condition is associated with FLNB p.Phe825fs (c.2474_2475del)?

FLNB p.Phe825fs (c.2474_2475del) is associated with spondylocarpotarsal synostosis syndrome (ClinVar).

How common is FLNB p.Phe825fs (c.2474_2475del) in the general population?

FLNB p.Phe825fs (c.2474_2475del) is very rare (popmax 0.0011%, sas) (gnomAD).

FLNB p.Phe825fs

c.2474_2475del · VCV4812939

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 16 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.46	GERP 2.6, phastCons 0.032

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 6.84e-05% 1/1,461,892 alleles · very rare

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: FLNB
Protein: p.Phe825fs
Coding: c.2474_2475del
MANE Select: NM_001457
Type: Deletion
Location: chr3:58110159 (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.Glu498fs Pathogenic ★ same condition
FLNB p.Gly1149fs Likely pathogenic ★ same condition
FLNB p.Ile1590fs 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-phe825fs (accessed [today's date]).

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