Is FLNB p.Arg969= (c.2907G>A) pathogenic?

FLNB p.Arg969= (c.2907G>A) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Low-frequency (popmax 2.42%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Arg969= (c.2907G>A)?

FLNB p.Arg969= (c.2907G>A) is associated with FLNB-Related Spectrum Disorders, connective tissue disorder (ClinVar).

How common is FLNB p.Arg969= (c.2907G>A) in the general population?

FLNB p.Arg969= (c.2907G>A) is low-frequency (popmax 2.42%, afr) (gnomAD).

FLNB p.Arg969=

c.2907G>A · rs138449267 · VCV346326

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.42%, 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 -1.4	GERP -5.4
Overall
CADD	1.289	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.42% African / African-American · 1,818/75,010 alleles

Filtering AF 2.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.29%

Overall 0.136% 2,188/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.42%	41
Admixed American	0.272%	368
Remaining individualsnot grpmax-eligible	0.237%	422
Middle Eastern	0.181%	551
European (non-Finnish)	0.00381%	26,223
South Asian	0.00329%	30,361

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.Arg969=
Coding: c.2907G>A
MANE Select: NM_001457
dbSNP: rs138449267
Type: single nucleotide variant
Location: chr3:58121284 (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

Also linked: connective tissue disorder

Similar variants

FLNB p.Arg969Gly Uncertain significance ★ ⚠ same residue
FLNB p.Arg969Ser Uncertain significance ★ ⚠ same residue
FLNB p.Phe161Cys Likely pathogenic ★★ same condition
FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.Gly496Cys Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Leu1440Pro 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-arg969 (accessed [today's date]).

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