Is FLNB p.Arg2016Gln (c.6047G>A) pathogenic?

FLNB p.Arg2016Gln (c.6047G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-03). AlphaMissense: likely benign (0.0833); Rare (popmax 0.421%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Arg2016Gln (c.6047G>A)?

FLNB p.Arg2016Gln (c.6047G>A) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Arg2016Gln (c.6047G>A) in the general population?

FLNB p.Arg2016Gln (c.6047G>A) is rare (popmax 0.421%, afr) (gnomAD).

What do computational predictors say about FLNB p.Arg2016Gln (c.6047G>A)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

FLNB p.Arg2016Gln

c.6047G>A · rs137885421 · VCV281765

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.421%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	29.0	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 0.421% African / African-American · 316/75,032 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.368%

Overall 0.0224% 362/1,613,870 alleles · rare exomes 203/1,461,620 · genomes 159/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.421%	237
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.0133%	7,502
East Asian	0.00223%	44,868
European (non-Finnish)	0.00195%	51,306
South Asian	0.0011%	91,058

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.Arg2016Gln
Coding: c.6047G>A
MANE Select: NM_001457
dbSNP: rs137885421
Type: single nucleotide variant
Location: chr3:58148808 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2016: 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

Disease context

FLNB-Related Spectrum Disorders

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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-arg2016gln (accessed [today's date]).

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