Is FLNB p.Ala1286Val (c.3857C>T) pathogenic?

FLNB p.Ala1286Val (c.3857C>T) is classified Benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1437); Common (popmax 9.94%, afr) — too common for a highly-penetrant pathogenic allele; Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Ala1286Val (c.3857C>T)?

FLNB p.Ala1286Val (c.3857C>T) is associated with FLNB-Related Spectrum Disorders, connective tissue disorder (ClinVar).

What do computational predictors say about FLNB p.Ala1286Val (c.3857C>T)?

AlphaMissense predicts likely benign (score 0.1437) — an in-silico prediction, not a clinical call.

FLNB p.Ala1286Val

Q: How common is FLNB p.Ala1286Val (c.3857C>T) in the general population?

FLNB p.Ala1286Val (c.3857C>T) is common (popmax 9.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3857C>T · rs62621997 · VCV258108

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1437 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.94%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.1437	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -7.70	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 1.1	GERP 0.58, phastCons 0.56
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 9.94% African / African-American · 7,456/75,022 alleles

Filtering AF 9.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.67%

Overall 0.524% 8,455/1,614,142 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.94%	10
Remaining individualsnot grpmax-eligible	0.739%	135
Admixed American	0.671%	149
Middle Eastern	0.644%	155
South Asian	0.0242%	4,140
European (non-Finnish)	0.00619%	16,165

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.Ala1286Val
Coding: c.3857C>T
MANE Select: NM_001457
dbSNP: rs62621997
Type: single nucleotide variant
Location: chr3:58124464 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1286: a β-strand; 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

Also linked: connective tissue disorder

Similar variants

FLNB p.Ala1286= Likely benign ★★ same residue
FLNB p.Ala1286Ser Uncertain significance ★ ⚠ same residue
FLNB p.Phe161Cys Likely pathogenic ★★ same condition
FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.Gly496Cys Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Leu1440Pro 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-ala1286val (accessed [today's date]).

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