Is FLNB p.Gly565Arg (c.1693G>A) pathogenic?

FLNB p.Gly565Arg (c.1693G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-08). AlphaMissense: likely pathogenic (0.6038); Ultra-rare (popmax 0.0117%, amr); Associated with Boomerang dysplasia.

What condition is associated with FLNB p.Gly565Arg (c.1693G>A)?

FLNB p.Gly565Arg (c.1693G>A) is associated with Boomerang dysplasia (ClinVar).

How common is FLNB p.Gly565Arg (c.1693G>A) in the general population?

FLNB p.Gly565Arg (c.1693G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Boomerang dysplasia inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FLNB p.Gly565Arg (c.1693G>A)?

AlphaMissense predicts likely pathogenic (score 0.6038) — an in-silico prediction, not a clinical call.

FLNB p.Gly565Arg

c.1693G>A · rs754869116 · VCV1047487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6038 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Boomerang dysplasia

Computational evidence

Protein change
AlphaMissense	0.6038	likely pathogenic
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -10.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	27.7	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 0.0117% Admixed American · 7/59,994 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00248% 40/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
African / African-American	0.004%	24,977
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00229%	43,706
South Asian	0.0011%	91,084

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.Gly565Arg
Coding: c.1693G>A
MANE Select: NM_001457
dbSNP: rs754869116
Type: single nucleotide variant
Location: chr3:58105162 (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

Boomerang dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Boomerang dysplasia (Orphanet):

Inheritance: Not applicable
Onset: Antenatal, Neonatal

Similar variants

FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB c.3724+4G>C Uncertain significance ★★ same condition
FLNB p.Arg2289His Uncertain significance ★★ ⚠ same condition
FLNB p.Arg999Gln Uncertain significance ★★ ⚠ same condition
FLNB p.Gly1022Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Gly1464Ala Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg 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-gly565arg (accessed [today's date]).

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