Is BFSP2 p.Ala296= (c.888T>G) pathogenic?

BFSP2 p.Ala296= (c.888T>G) is classified Likely benign in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-14). Ultra-rare (popmax 0.0362%, sas); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Ala296= (c.888T>G)?

BFSP2 p.Ala296= (c.888T>G) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Ala296= (c.888T>G) in the general population?

BFSP2 p.Ala296= (c.888T>G) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

BFSP2 p.Ala296=

c.888T>G · rs199694156 · VCV744871

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Conditions

cataract 12 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.68	GERP -3.1, phastCons 1
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% South Asian · 33/91,076 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00223% 36/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	8.47e-05%	1,179,994

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.Ala296=
Coding: c.888T>G
dbSNP: rs199694156
Type: single nucleotide variant
Location: chr3:133450461 (GRCh38)

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

Disease context

cataract 12 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ala296 (accessed [today's date]).

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