Is FLNB p.Ala858Ser (c.2572G>T) pathogenic?

FLNB p.Ala858Ser (c.2572G>T) is classified Likely benign in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0706); Ultra-rare (popmax 0.0267%, amr); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Ala858Ser (c.2572G>T)?

FLNB p.Ala858Ser (c.2572G>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLNB p.Ala858Ser (c.2572G>T) in the general population?

FLNB p.Ala858Ser (c.2572G>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about FLNB p.Ala858Ser (c.2572G>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

FLNB p.Ala858Ser

c.2572G>T · rs751338334 · VCV1484937

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -5.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -4.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	18.57	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 0.0267% Admixed American · 16/60,006 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000992% 16/1,613,556 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.Ala858Ser
Coding: c.2572G>T
MANE Select: NM_001457
dbSNP: rs751338334
Type: single nucleotide variant
Location: chr3:58111878 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB

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

FLNB p.Ala858Pro Uncertain significance ★ ⚠ same residue
FLNB c.4862-3C>T Uncertain significance ★★ same condition
FLNB p.Ala1191Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1191Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1391Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1427Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1608Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1704Ser 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-ala858ser (accessed [today's date]).

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