Is FLNB p.Asp288= (c.864C>T) pathogenic?

FLNB p.Asp288= (c.864C>T) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.033%, mid); Associated with connective tissue disorder.

What condition is associated with FLNB p.Asp288= (c.864C>T)?

FLNB p.Asp288= (c.864C>T) is associated with connective tissue disorder (ClinVar).

How common is FLNB p.Asp288= (c.864C>T) in the general population?

FLNB p.Asp288= (c.864C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

FLNB p.Asp288=

c.864C>T · rs141151998 · VCV346306

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -9.8	GERP -5.4
Overall
CADD	6.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.0168% 271/1,614,106 alleles · ultra-rare exomes 245/1,461,860 · genomes 26/152,246 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
South Asian	0.0275%	3,643
Remaining individualsnot grpmax-eligible	0.0256%	3,906
European (non-Finnish)	0.0179%	5,592
Finnishnot grpmax-eligible	0.0141%	7,114
Admixed American	0.0117%	8,572
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Asp288=
Coding: c.864C>T
MANE Select: NM_001457
dbSNP: rs141151998
Type: single nucleotide variant
Location: chr3:58094912 (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

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

Similar variants

FLNB p.Asp288Glu 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-asp288 (accessed [today's date]).

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