Is BFSP2 p.Glu289Lys (c.865G>A) pathogenic?

BFSP2 p.Glu289Lys (c.865G>A) is classified Conflicting classifications of pathogenicity in BFSP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-27). AlphaMissense: likely benign (0.1159); Ultra-rare (popmax 0.063%, nfe); Associated with BFSP2-related disorder.

What condition is associated with BFSP2 p.Glu289Lys (c.865G>A)?

BFSP2 p.Glu289Lys (c.865G>A) is associated with BFSP2-related disorder, cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Glu289Lys (c.865G>A) in the general population?

BFSP2 p.Glu289Lys (c.865G>A) is ultra-rare (popmax 0.063%, nfe) (gnomAD).

What do computational predictors say about BFSP2 p.Glu289Lys (c.865G>A)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

BFSP2 p.Glu289Lys

c.865G>A · rs145444931 · VCV343412

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.063%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BFSP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.708	pathogenic-leaning
SaProt	LLR -8.35	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	23.2	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 0.063% European (non-Finnish) · 743/1,180,022 alleles

Filtering AF 0.0592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0577%

Overall 0.0495% 799/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.063%	1,588
Admixed American	0.0417%	2,400
Remaining individualsnot grpmax-eligible	0.0272%	3,675
African / African-American	0.0147%	6,809
South Asian	0.0022%	45,546
Finnishnot grpmax-eligible	0.00156%	64,008

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: BFSP2
Protein: p.Glu289Lys
Coding: c.865G>A
dbSNP: rs145444931
Type: single nucleotide variant
Location: chr3:133450438 (GRCh38)

Full BFSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BFSP2-related disorder

Also linked: cataract 12 multiple types

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/bfsp2-p-glu289lys (accessed [today's date]).

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