Is FLNB p.Pro1603Ser (c.4807C>T) pathogenic?

FLNB p.Pro1603Ser (c.4807C>T) is classified Pathogenic in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.7216); Absent from gnomAD v4.1; Associated with atelosteogenesis type I.

What condition is associated with FLNB p.Pro1603Ser (c.4807C>T)?

FLNB p.Pro1603Ser (c.4807C>T) is associated with atelosteogenesis type I (ClinVar).

How common is FLNB p.Pro1603Ser (c.4807C>T) in the general population?

FLNB p.Pro1603Ser (c.4807C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNB p.Pro1603Ser (c.4807C>T)?

AlphaMissense predicts likely pathogenic (score 0.7216) — an in-silico prediction, not a clinical call.

FLNB p.Pro1603Ser

c.4807C>T · rs2107224894 · VCV1685823

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7216 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atelosteogenesis type I

Computational evidence

Protein change
AlphaMissense	0.7216	likely pathogenic ✓ concordant with ClinVar
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -13.60	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 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,301 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNB
Protein: p.Pro1603Ser
Coding: c.4807C>T
MANE Select: NM_001457
dbSNP: rs2107224894
Type: single nucleotide variant
Location: chr3:58136114 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1603: a β-strand; a UniProt-annotated variant site (in lrs)

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

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.Ala259Val 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

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-pro1603ser (accessed [today's date]).

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