Is FLNB p.Pro1336Ser (c.4006C>T) pathogenic?

FLNB p.Pro1336Ser (c.4006C>T) is classified Uncertain significance in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1164); Absent from gnomAD v4.1; Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Pro1336Ser (c.4006C>T)?

FLNB p.Pro1336Ser (c.4006C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Pro1336Ser (c.4006C>T) in the general population?

FLNB p.Pro1336Ser (c.4006C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNB p.Pro1336Ser (c.4006C>T)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

FLNB p.Pro1336Ser

c.4006C>T · rs767618168 · VCV346340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.596	indeterminate
SaProt	LLR -9.09	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 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	24.6	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

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.Pro1336Ser
Coding: c.4006C>T
MANE Select: NM_001457
dbSNP: rs767618168
Type: single nucleotide variant
Location: chr3:58125688 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1336: an α-helix; the 'interaction with fblp1' region

Full FLNB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FLNB-Related Spectrum Disorders

Similar variants

FLNB p.Pro1336Thr Uncertain significance ★★ ⚠ same residue
FLNB p.Pro1336= Likely benign ★ same residue
FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Leu1440Pro Uncertain significance ★★ ⚠ same condition
FLNB p.Pro396Ser Uncertain significance ★★ ⚠ same condition
FLNB p.Ser1096Phe 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-pro1336ser (accessed [today's date]).

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