Is FLNB p.Val3= (c.9A>G) pathogenic?

FLNB p.Val3= (c.9A>G) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-29). Ultra-rare (popmax 0.0549%, eas); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Val3= (c.9A>G)?

FLNB p.Val3= (c.9A>G) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Val3= (c.9A>G) in the general population?

FLNB p.Val3= (c.9A>G) is ultra-rare (popmax 0.0549%, eas) (gnomAD).

FLNB p.Val3=

c.9A>G · rs199846967 · VCV516180

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, eas)

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 -0.23	GERP -3.5, phastCons 0.014
Overall
CADD	9.734	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0549% East Asian · 24/43,702 alleles

Filtering AF 0.0378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0322%

Overall 0.00213% 34/1,595,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0549%	1,821
Middle Eastern	0.0212%	4,722
South Asian	0.00674%	14,847
Remaining individualsnot grpmax-eligible	0.00485%	20,606

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.Val3=
Coding: c.9A>G
MANE Select: NM_001457
dbSNP: rs199846967
Type: single nucleotide variant
Location: chr3:58008573 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 3: the 'actin-binding' region

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

Disease context

FLNB-Related Spectrum Disorders

Similar variants

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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-val3 (accessed [today's date]).

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