Is FLNB p.Arg2010His (c.6029G>A) pathogenic?

FLNB p.Arg2010His (c.6029G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-21). AlphaMissense: likely benign (0.0809); Very rare (popmax 0.00525%, nfe).

How common is FLNB p.Arg2010His (c.6029G>A) in the general population?

FLNB p.Arg2010His (c.6029G>A) is very rare (popmax 0.00525%, nfe) (gnomAD).

What do computational predictors say about FLNB p.Arg2010His (c.6029G>A)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

FLNB p.Arg2010His

c.6029G>A · rs188216614 · VCV1058417

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
REVEL	0.428	indeterminate
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.65, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,180,038 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00446% 72/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,033
East Asian	0.00446%	22,436
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0032%	31,256
Admixed American	0.00167%	60,028
African / African-American	0.00133%	75,036

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.Arg2010His
Coding: c.6029G>A
MANE Select: NM_001457
dbSNP: rs188216614
Type: single nucleotide variant
Location: chr3:58148790 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2010: a β-strand; the 'interaction with the cytoplasmic tail of gp1ba' region

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

Similar variants

FLNB p.Arg2010Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNB p.Arg2010= Likely benign ★ same residue
FLNB c.4390+2T>C Pathogenic/Likely pathogenic ★★ same type
FLNB c.5110-1G>A Likely pathogenic ★★ same type
FLNB p.Arg1463Ter Pathogenic/Likely pathogenic ★★ same type
FLNB p.Arg1948Ter Pathogenic ★★ same type
FLNB p.Arg649Ter Pathogenic ★★ same type
FLNB p.Asp167Gly Likely pathogenic ★★ ⚠ same type

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-arg2010his (accessed [today's date]).

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