Is FLNB p.Arg1607Ter (c.4819C>T) pathogenic?

FLNB p.Arg1607Ter (c.4819C>T) is classified Likely pathogenic in FLNB (ClinVar, Single submitter, 4 submitters; last evaluated 2020-10-26). Very rare (popmax 0.0022%, sas); Associated with spondylocarpotarsal synostosis syndrome.

What condition is associated with FLNB p.Arg1607Ter (c.4819C>T)?

FLNB p.Arg1607Ter (c.4819C>T) is associated with spondylocarpotarsal synostosis syndrome (ClinVar).

How common is FLNB p.Arg1607Ter (c.4819C>T) in the general population?

FLNB p.Arg1607Ter (c.4819C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

FLNB p.Arg1607Ter

c.4819C>T · rs80356520 · VCV6397

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 28 of 46
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Overall
CADD	43.0	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 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00112% 18/1,613,780 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,434
Finnishnot grpmax-eligible	0.00157%	63,892
European (non-Finnish)	0.00119%	84,286

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.Arg1607Ter
Coding: c.4819C>T
MANE Select: NM_001457
dbSNP: rs80356520
Type: single nucleotide variant
Location: chr3:58136126 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1607: 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.Arg1607Gln Likely benign ★ same residue
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

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-arg1607ter (accessed [today's date]).

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