Is FLNB p.His560Arg (c.1679A>G) pathogenic?

FLNB p.His560Arg (c.1679A>G) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-09-20). AlphaMissense: likely benign (0.0855); Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.His560Arg (c.1679A>G)?

FLNB p.His560Arg (c.1679A>G) is associated with Inborn genetic diseases, spondylocarpotarsal synostosis syndrome (ClinVar).

How common is FLNB p.His560Arg (c.1679A>G) in the general population?

FLNB p.His560Arg (c.1679A>G) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about FLNB p.His560Arg (c.1679A>G)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

FLNB p.His560Arg

c.1679A>G · rs749965480 · VCV392383

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -5.89	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 8	GERP 2.6, phastCons 0.98
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	23.6	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 0.00769% South Asian · 7/91,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000558% 9/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
African / African-American	0.00133%	74,942
European (non-Finnish)	8.47e-05%	1,180,057

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.His560Arg
Coding: c.1679A>G
MANE Select: NM_001457
dbSNP: rs749965480
Type: single nucleotide variant
Location: chr3:58105148 (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

Also linked: spondylocarpotarsal synostosis syndrome

Similar variants

FLNB p.His560= Likely benign ★ same residue
FLNB p.Arg1948Ter Pathogenic ★★ same condition
FLNB p.Arg649Ter Pathogenic ★★ same condition
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB c.3724+4G>C Uncertain significance ★★ same condition
FLNB c.4862-3C>T Uncertain significance ★★ same condition
FLNB p.Ala1191Thr 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-his560arg (accessed [today's date]).

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