Is FLNB p.Ile2547= (c.7641C>T) pathogenic?

FLNB p.Ile2547= (c.7641C>T) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.028%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Ile2547= (c.7641C>T)?

FLNB p.Ile2547= (c.7641C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Ile2547= (c.7641C>T) in the general population?

FLNB p.Ile2547= (c.7641C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

FLNB p.Ile2547=

c.7641C>T · rs139582437 · VCV757632

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Conditions

FLNB-Related Spectrum Disorders

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 -8.4	GERP -4.3
Overall
CADD	1.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/75,022 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00508% 82/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,572
Admixed American	0.005%	20,003
European (non-Finnish)	0.00458%	21,852
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Ile2547=
Coding: c.7641C>T
MANE Select: NM_001457
dbSNP: rs139582437
Type: single nucleotide variant
Location: chr3:58170594 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2547: a β-strand; the 'interaction with inppl1' region; the 'self-association site, tail' region; the 'interaction with flna 2' region

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

Disease context

FLNB-Related Spectrum Disorders

Similar variants

FLNB p.Ile2547Thr Uncertain significance ⚠ same residue
FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Leu1440Pro Uncertain significance ★★ ⚠ same condition
FLNB p.Pro396Ser Uncertain significance ★★ ⚠ same condition
FLNB p.Ser1096Phe Uncertain significance ★★ ⚠ same condition
FLNB p.Ser188Cys 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-ile2547 (accessed [today's date]).

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