Is FLNB p.Phe2023Ser (c.6068T>C) pathogenic?

FLNB p.Phe2023Ser (c.6068T>C) is classified Likely pathogenic in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-23). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with FLNB-related disorder.

What condition is associated with FLNB p.Phe2023Ser (c.6068T>C)?

FLNB p.Phe2023Ser (c.6068T>C) is associated with FLNB-related disorder (ClinVar).

How common is FLNB p.Phe2023Ser (c.6068T>C) in the general population?

FLNB p.Phe2023Ser (c.6068T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNB p.Phe2023Ser (c.6068T>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

FLNB p.Phe2023Ser

c.6068T>C · rs2471206868 · VCV2711306

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FLNB-related disorder

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in FLNB
REVEL	0.98	strongly pathogenic-leaning
SaProt	LLR -17.26	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 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	28.1	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.Phe2023Ser
Coding: c.6068T>C
MANE Select: NM_001457
dbSNP: rs2471206868
Type: single nucleotide variant
Location: chr3:58148829 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2023: a β-strand; the 'interaction with the cytoplasmic tail of gp1ba' region

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

Disease context

FLNB-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Arg649Ter Pathogenic ★★ same condition
FLNB p.Glu227Lys Pathogenic ★★ same condition
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB p.Tyr1395Ter Pathogenic/Likely pathogenic ★★ same condition
FLNB p.Arg1438Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Arg2101Leu Uncertain significance ★★ ⚠ same condition
FLNB p.Arg566Pro 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-phe2023ser (accessed [today's date]).

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