Is BFSP2 p.Ala25= (c.75G>A) pathogenic?

BFSP2 p.Ala25= (c.75G>A) is classified Benign in BFSP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-14). Low-frequency (popmax 2.15%, eas); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Ala25= (c.75G>A)?

BFSP2 p.Ala25= (c.75G>A) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Ala25= (c.75G>A) in the general population?

BFSP2 p.Ala25= (c.75G>A) is low-frequency (popmax 2.15%, eas) (gnomAD).

BFSP2 p.Ala25=

c.75G>A · rs146992682 · VCV343398

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.15%, eas)

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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.6
Overall
CADD	0.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.15% East Asian · 967/44,878 alleles

Filtering AF 2.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 2%

Overall 0.119% 1,924/1,614,140 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.15%	46
Ashkenazi Jewishnot grpmax-eligible	0.993%	101
Remaining individualsnot grpmax-eligible	0.371%	269
South Asian	0.222%	451
Middle Eastern	0.148%	674
African / African-American	0.0293%	3,412
Admixed American	0.0283%	3,531
European (non-Finnish)	0.0153%	6,519

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.Ala25=
Coding: c.75G>A
MANE Select: NM_003571
dbSNP: rs146992682
Type: single nucleotide variant
Location: chr3:133400158 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 25: the 'disordered' region; the 'head' region

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

Similar variants

BFSP2 p.Arg4Lys Uncertain significance ★★ ⚠ same condition
BFSP2 p.Arg5Ter Uncertain significance ★★ same condition
BFSP2 p.Arg72His Uncertain significance ★★ ⚠ same condition
BFSP2 p.Glu141Ala Uncertain significance ★★ ⚠ same condition
BFSP2 p.Glu289Asp Uncertain significance ★★ ⚠ same condition
BFSP2 p.Leu153Gln Uncertain significance ★★ ⚠ same condition
BFSP2 c.572+160A>G Benign ★★ same condition
BFSP2 c.730-7T>C Benign/Likely benign ★★ 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/bfsp2-p-ala25 (accessed [today's date]).

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