Is FLNB p.Arg818Gln (c.2453G>A) pathogenic?

FLNB p.Arg818Gln (c.2453G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0981); Rare (popmax 0.201%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Arg818Gln (c.2453G>A)?

FLNB p.Arg818Gln (c.2453G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FLNB p.Arg818Gln (c.2453G>A) in the general population?

FLNB p.Arg818Gln (c.2453G>A) is rare (popmax 0.201%, nfe) (gnomAD).

What do computational predictors say about FLNB p.Arg818Gln (c.2453G>A)?

AlphaMissense predicts likely benign (score 0.0981) — an in-silico prediction, not a clinical call.

FLNB p.Arg818Gln

c.2453G>A · rs151259375 · VCV388816

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0981 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.201%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0981	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -6.39	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	27.3	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 0.201% European (non-Finnish) · 2,366/1,180,026 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.191%

Overall 0.155% 2,506/1,614,190 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.201%	499
Remaining individualsnot grpmax-eligible	0.11%	906
Middle Eastern	0.0825%	1,212
African / African-American	0.0373%	2,680
Admixed American	0.0267%	3,751
South Asian	0.0187%	5,358
Finnishnot grpmax-eligible	0.00625%	16,010
East Asian	0.00223%	44,888

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.Arg818Gln
Coding: c.2453G>A
MANE Select: NM_001457
dbSNP: rs151259375
Type: single nucleotide variant
Location: chr3:58110139 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Arg818Ter Pathogenic ★ same residue
FLNB c.4862-3C>T Uncertain significance ★★ same condition
FLNB p.Ala1191Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1191Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1391Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1427Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1608Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1704Ser 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-arg818gln (accessed [today's date]).

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