Is BFSP2 p.Ser325Pro (c.973T>C) pathogenic?

BFSP2 p.Ser325Pro (c.973T>C) is classified Uncertain significance in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-25). AlphaMissense: likely pathogenic (0.6607); Absent from gnomAD v4.1; Associated with cataract 12 multiple types.

What condition is associated with BFSP2 p.Ser325Pro (c.973T>C)?

BFSP2 p.Ser325Pro (c.973T>C) is associated with cataract 12 multiple types (ClinVar).

How common is BFSP2 p.Ser325Pro (c.973T>C) in the general population?

BFSP2 p.Ser325Pro (c.973T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BFSP2 p.Ser325Pro (c.973T>C)?

AlphaMissense predicts likely pathogenic (score 0.6607) — an in-silico prediction, not a clinical call.

BFSP2 p.Ser325Pro

c.973T>C · VCV4743599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 12 multiple types

Computational evidence

Protein change
AlphaMissense	0.6607	likely pathogenic · top 7% in BFSP2
REVEL	0.543	indeterminate
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.065	GERP -3.6, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	19.4	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

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: BFSP2
Protein: p.Ser325Pro
Coding: c.973T>C
MANE Select: NM_003571
Type: single nucleotide variant
Location: chr3:133466909 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 325: 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.Ser325Ala Uncertain significance ★ ⚠ same residue
BFSP2 p.Ser325Leu 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

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-ser325pro (accessed [today's date]).

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