Is FLNB c.2575+12C>T pathogenic?

FLNB c.2575+12C>T is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-04-18). Very rare (popmax 0.00668%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB c.2575+12C>T?

FLNB c.2575+12C>T is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB c.2575+12C>T in the general population?

FLNB c.2575+12C>T is very rare (popmax 0.00668%, afr) (gnomAD).

FLNB c.2575+12C>T

rs750560502 · VCV346325

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.1	GERP -3.7
Non-coding constraint	Z 2.16	1 kb window · o/e 0.84 · regional · uncalibrated
Overall
CADD	0.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,798 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00205% 33/1,608,762 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,960
South Asian	0.0055%	18,192
Remaining individualsnot grpmax-eligible	0.00482%	20,766
Admixed American	0.00333%	30,001
European (non-Finnish)	0.00153%	65,294

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
Coding: c.2575+12C>T
MANE Select: NM_001457
dbSNP: rs750560502
Type: single nucleotide variant
Location: chr3:58111893 (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

FLNB-Related Spectrum Disorders

Similar variants

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
FLNB p.Tyr63His 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-c-2575-plus-12c-t (accessed [today's date]).

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