Is FLNB p.Ser2487Phe (c.7460C>T) pathogenic?

FLNB p.Ser2487Phe (c.7460C>T) is classified Likely benign in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-07). AlphaMissense: ambiguous (0.3858); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Ser2487Phe (c.7460C>T)?

FLNB p.Ser2487Phe (c.7460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLNB p.Ser2487Phe (c.7460C>T) in the general population?

FLNB p.Ser2487Phe (c.7460C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about FLNB p.Ser2487Phe (c.7460C>T)?

AlphaMissense predicts ambiguous (score 0.3858) — an in-silico prediction, not a clinical call.

FLNB p.Ser2487Phe

c.7460C>T · rs771879974 · VCV3000866

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3858	ambiguous
REVEL	0.654	pathogenic-leaning
SaProt	LLR -11.11	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.0178% East Asian · 8/44,896 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000496% 8/1,614,098 alleles · ultra-rare

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.Ser2487Phe
Coding: c.7460C>T
MANE Select: NM_001457
dbSNP: rs771879974
Type: single nucleotide variant
Location: chr3:58169632 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2487: the 'interaction with inppl1' region; the 'self-association site, tail' region; the 'hinge 2' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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-ser2487phe (accessed [today's date]).

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