Is FLNB p.Ser2388Pro (c.7162T>C) pathogenic?

FLNB p.Ser2388Pro (c.7162T>C) is classified Uncertain significance in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-25). AlphaMissense: likely pathogenic (0.8718); Absent from gnomAD v4.1.

How common is FLNB p.Ser2388Pro (c.7162T>C) in the general population?

FLNB p.Ser2388Pro (c.7162T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNB p.Ser2388Pro (c.7162T>C)?

AlphaMissense predicts likely pathogenic (score 0.8718) — an in-silico prediction, not a clinical call.

FLNB p.Ser2388Pro

c.7162T>C · rs1172338396 · VCV1306340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8718 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8718	likely pathogenic
REVEL	0.618	indeterminate
SaProt	LLR -12.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ser2388Pro
Coding: c.7162T>C
MANE Select: NM_001457
dbSNP: rs1172338396
Type: single nucleotide variant
Location: chr3:58163294 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2388: a β-strand; the 'interaction with inppl1' region

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

Similar variants

FLNB p.Ser2388= Conflicting classifications of pathogenicity ★ same residue
FLNB c.4390+2T>C Pathogenic/Likely pathogenic ★★ same type
FLNB c.5110-1G>A Likely pathogenic ★★ same type
FLNB p.Arg1463Ter Pathogenic/Likely pathogenic ★★ same type
FLNB p.Arg1948Ter Pathogenic ★★ same type
FLNB p.Arg649Ter Pathogenic ★★ same type
FLNB p.Asp167Gly Likely pathogenic ★★ same type
FLNB p.Glu227Lys Pathogenic ★★ same type

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-ser2388pro (accessed [today's date]).

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