Is BFSP2 p.His123= (c.369C>T) pathogenic?

BFSP2 p.His123= (c.369C>T) is classified Benign in BFSP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-23). Low-frequency (popmax 3.51%, afr); Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.His123= (c.369C>T)?

BFSP2 p.His123= (c.369C>T) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.His123= (c.369C>T) in the general population?

BFSP2 p.His123= (c.369C>T) is low-frequency (popmax 3.51%, afr) (gnomAD).

BFSP2 p.His123=

c.369C>T · rs34163197 · VCV343404

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.51%, afr)

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 -13	GERP -3.4
Overall
CADD	0.819	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.51% African / African-American · 2,630/75,020 alleles

Filtering AF 3.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.35%

Overall 0.194% 3,134/1,614,020 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.51%	29
Remaining individualsnot grpmax-eligible	0.277%	361
Admixed American	0.213%	469
Middle Eastern	0.148%	674
European (non-Finnish)	0.0153%	6,556
South Asian	0.00988%	10,121
East Asian	0.00891%	11,220
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.His123=
Coding: c.369C>T
MANE Select: NM_003571
dbSNP: rs34163197
Type: single nucleotide variant
Location: chr3:133400452 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 123: 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.His123Arg Uncertain significance ★ ⚠ same residue
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

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-his123 (accessed [today's date]).

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