Is FLNB p.Arg2004Ter (c.6010C>T) pathogenic?

FLNB p.Arg2004Ter (c.6010C>T) is classified Pathogenic in FLNB (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-01). Very rare (popmax 0.00446%, eas); Associated with spondylocarpotarsal synostosis syndrome.

What condition is associated with FLNB p.Arg2004Ter (c.6010C>T)?

FLNB p.Arg2004Ter (c.6010C>T) is associated with spondylocarpotarsal synostosis syndrome (ClinVar).

How common is FLNB p.Arg2004Ter (c.6010C>T) in the general population?

FLNB p.Arg2004Ter (c.6010C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

FLNB p.Arg2004Ter

c.6010C>T · rs121908897 · VCV6407

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

spondylocarpotarsal synostosis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 36 of 46
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.5, phastCons 0.99
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000479% 7/1,461,844 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
European (non-Finnish)	0.000424%	236,008

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.Arg2004Ter
Coding: c.6010C>T
MANE Select: NM_001457
dbSNP: rs121908897
Type: single nucleotide variant
Location: chr3:58148771 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2004: an α-helix; the 'interaction with the cytoplasmic tail of gp1ba' region

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 c.3724+4G>C Uncertain significance ★★ same condition
FLNB p.Arg1545Gln Uncertain significance ★★ ⚠ same condition
FLNB p.Arg2289His Uncertain significance ★★ ⚠ same condition
FLNB p.Arg999Gln 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-arg2004ter (accessed [today's date]).

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