Is BFSP1 p.Lys254= (c.762A>G) pathogenic?

BFSP1 p.Lys254= (c.762A>G) is classified Benign/Likely benign in BFSP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-01). Rare (popmax 0.674%, afr); Associated with cataract 33.

What condition is associated with BFSP1 p.Lys254= (c.762A>G)?

BFSP1 p.Lys254= (c.762A>G) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Lys254= (c.762A>G) in the general population?

BFSP1 p.Lys254= (c.762A>G) is rare (popmax 0.674%, afr) (gnomAD).

BFSP1 p.Lys254=

c.762A>G · rs35042144 · VCV474091

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.674%, afr)

Conditions

cataract 33

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 0.66	GERP -2.8, phastCons 1
Overall
CADD	5.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.674% African / African-American · 506/75,028 alleles

Filtering AF 0.626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.607%

Overall 0.0338% 545/1,614,140 alleles · rare exomes 241/1,461,884 · genomes 304/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.674%	148
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed American	0.0217%	4,617
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000763%	131,112

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: BFSP1
Protein: p.Lys254=
Coding: c.762A>G
MANE Select: NM_001195
dbSNP: rs35042144
Type: single nucleotide variant
Location: chr20:17499014 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 254: the if rod domain; the 'coil 2' region

Full BFSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same condition
BFSP1 p.Arg69Trp Uncertain significance ★★ same condition
BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile271Thr Uncertain significance ★★ ⚠ same condition
BFSP1 p.Leu68Phe Uncertain significance ★★ 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/bfsp1-p-lys254 (accessed [today's date]).

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