Is FLNB p.Ser1529Pro (c.4585T>C) pathogenic?

FLNB p.Ser1529Pro (c.4585T>C) is classified Uncertain significance in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-11). AlphaMissense: likely benign (0.0935); Very rare (popmax 0.00237%, nfe); Associated with atelosteogenesis type I.

What condition is associated with FLNB p.Ser1529Pro (c.4585T>C)?

FLNB p.Ser1529Pro (c.4585T>C) is associated with atelosteogenesis type I (ClinVar).

How common is FLNB p.Ser1529Pro (c.4585T>C) in the general population?

FLNB p.Ser1529Pro (c.4585T>C) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about FLNB p.Ser1529Pro (c.4585T>C)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

FLNB p.Ser1529Pro

c.4585T>C · rs770433500 · VCV1030456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

atelosteogenesis type I

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.46	indeterminate
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.47	GERP -2, phastCons 0.12
Regional constraint	o/e 0.69	unconstrained · MANE · 3,301 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,004 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00173% 28/1,614,160 alleles · very rare exomes 28/1,461,864 · genomes 0/152,296 · joint denominator

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.Ser1529Pro
Coding: c.4585T>C
MANE Select: NM_001457
dbSNP: rs770433500
Type: single nucleotide variant
Location: chr3:58134686 (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

atelosteogenesis type I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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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-ser1529pro (accessed [today's date]).

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