Is FLNB p.Ser1088= (c.3264C>T) pathogenic?

FLNB p.Ser1088= (c.3264C>T) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-21). Low-frequency (popmax 1.02%, afr); Associated with connective tissue disorder.

What condition is associated with FLNB p.Ser1088= (c.3264C>T)?

FLNB p.Ser1088= (c.3264C>T) is associated with connective tissue disorder (ClinVar).

How common is FLNB p.Ser1088= (c.3264C>T) in the general population?

FLNB p.Ser1088= (c.3264C>T) is low-frequency (popmax 1.02%, afr) (gnomAD).

FLNB p.Ser1088=

c.3264C>T · rs112864468 · VCV593766

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5.4
Overall
CADD	0.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.02% African / African-American · 767/75,040 alleles

Filtering AF 0.962% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.938%

Overall 0.0835% 1,348/1,614,112 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Middle Eastern	0.511%	196
South Asian	0.212%	472
Remaining individualsnot grpmax-eligible	0.162%	619
Admixed American	0.055%	1,819
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
European (non-Finnish)	0.018%	5,566
East Asian	0.00223%	44,886

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.Ser1088=
Coding: c.3264C>T
MANE Select: NM_001457
dbSNP: rs112864468
Type: single nucleotide variant
Location: chr3:58123230 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1088: a β-strand

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Ser1088Tyr Uncertain significance ★ ⚠ same residue
FLNB p.Phe161Cys Likely pathogenic ★★ same condition
FLNB p.Gly496Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Thr1003Met Uncertain significance ★★ ⚠ same condition
FLNB p.Thr1579Ile Uncertain significance ★★ ⚠ same condition
FLNB c.1611-4G>A Benign ★★ same condition
FLNB c.292+8C>A Benign/Likely benign ★★ same condition
FLNB c.4222+8A>G Benign/Likely benign ★★ 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-ser1088 (accessed [today's date]).

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