Is BFSP2 p.Leu174= (c.522C>T) pathogenic?

BFSP2 p.Leu174= (c.522C>T) is classified Likely benign in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-25). Very rare (popmax 0.00169%, nfe); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Leu174= (c.522C>T)?

BFSP2 p.Leu174= (c.522C>T) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Leu174= (c.522C>T) in the general population?

BFSP2 p.Leu174= (c.522C>T) is very rare (popmax 0.00169%, nfe) (gnomAD).

BFSP2 p.Leu174=

c.522C>T · rs375822049 · VCV1623008

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

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 0.17	GERP 0.7, phastCons 0.51
Overall
CADD	6.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,034 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00124% 20/1,613,944 alleles · very 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: BFSP2
Protein: p.Leu174=
Coding: c.522C>T
MANE Select: NM_003571
dbSNP: rs375822049
Type: single nucleotide variant
Location: chr3:133447349 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 174: the if rod domain

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-leu174 (accessed [today's date]).

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