Is BFSP1 p.Glu375Asp (c.1125G>T) pathogenic?

BFSP1 p.Glu375Asp (c.1125G>T) is classified Benign/Likely benign in BFSP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-04). AlphaMissense: likely benign (0.1069); Low-frequency (popmax 3.72%, afr); Associated with cataract 33.

What condition is associated with BFSP1 p.Glu375Asp (c.1125G>T)?

BFSP1 p.Glu375Asp (c.1125G>T) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Glu375Asp (c.1125G>T) in the general population?

BFSP1 p.Glu375Asp (c.1125G>T) is low-frequency (popmax 3.72%, afr) (gnomAD).

What do computational predictors say about BFSP1 p.Glu375Asp (c.1125G>T)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

BFSP1 p.Glu375Asp

c.1125G>T · rs139124891 · VCV474087

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.72%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 33

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.77, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	19.76	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.72% African / African-American · 2,792/75,032 alleles

Filtering AF 3.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.56%

Overall 0.192% 3,105/1,614,188 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.72%	27
Remaining individualsnot grpmax-eligible	0.232%	431
Admixed American	0.212%	473
Middle Eastern	0.099%	1,010
South Asian	0.00659%	15,181
European (non-Finnish)	0.00246%	40,691

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.Glu375Asp
Coding: c.1125G>T
MANE Select: NM_001195
dbSNP: rs139124891
Type: single nucleotide variant
Location: chr20:17494947 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 375: the 'tail' 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.Glu375Ter Uncertain significance ★ same residue
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

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-glu375asp (accessed [today's date]).

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