Is FLNB p.Pro1882= (c.5646G>A) pathogenic?

FLNB p.Pro1882= (c.5646G>A) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.66%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Pro1882= (c.5646G>A)?

FLNB p.Pro1882= (c.5646G>A) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Pro1882= (c.5646G>A) in the general population?

FLNB p.Pro1882= (c.5646G>A) is low-frequency (popmax 1.66%, afr) (gnomAD).

FLNB p.Pro1882=

c.5646G>A · rs114882667 · VCV258115

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.66%, 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 -0.67	GERP -3.8, phastCons 0.009
Overall
CADD	11.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.66% African / African-American · 1,243/75,010 alleles

Filtering AF 1.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.55%

Overall 0.0931% 1,503/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.66%	60
Remaining individualsnot grpmax-eligible	0.144%	694
Admixed American	0.135%	741
Middle Eastern	0.0495%	2,020
European (non-Finnish)	0.00678%	14,750
South Asian	0.00439%	22,770
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00156%	64,034

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.Pro1882=
Coding: c.5646G>A
MANE Select: NM_001457
dbSNP: rs114882667
Type: single nucleotide variant
Location: chr3:58146911 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1882: the 'interaction with the cytoplasmic tail of gp1ba' 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.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-p-pro1882 (accessed [today's date]).

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