Is BFSP1 p.Thr10Pro (c.28A>C) pathogenic?

BFSP1 p.Thr10Pro (c.28A>C) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). AlphaMissense: likely benign (0.2346); Absent from gnomAD v4.1; Associated with cataract 33.

What condition is associated with BFSP1 p.Thr10Pro (c.28A>C)?

BFSP1 p.Thr10Pro (c.28A>C) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Thr10Pro (c.28A>C) in the general population?

BFSP1 p.Thr10Pro (c.28A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BFSP1 p.Thr10Pro (c.28A>C)?

AlphaMissense predicts likely benign (score 0.2346) — an in-silico prediction, not a clinical call.

BFSP1 p.Thr10Pro

c.28A>C · VCV3664013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2346 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 33

Computational evidence

Protein change
AlphaMissense	0.2346	likely benign
REVEL	0.424	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -4.7, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BFSP1
Protein: p.Thr10Pro
Coding: c.28A>C
MANE Select: NM_001195
Type: single nucleotide variant
Location: chr20:17531302 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 10: the 'head' 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.Thr10= Likely benign ★ 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-thr10pro (accessed [today's date]).

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