Is BFSP1 p.Leu72Pro (c.215T>C) pathogenic?

BFSP1 p.Leu72Pro (c.215T>C) is classified Likely pathogenic in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-19). AlphaMissense: likely pathogenic (0.823); Very rare (popmax 0.000286%, nfe); Associated with cataract 33.

What condition is associated with BFSP1 p.Leu72Pro (c.215T>C)?

BFSP1 p.Leu72Pro (c.215T>C) is associated with cataract 33 (ClinVar).

How common is BFSP1 p.Leu72Pro (c.215T>C) in the general population?

BFSP1 p.Leu72Pro (c.215T>C) is very rare (popmax 0.000286%, nfe) (gnomAD).

What do computational predictors say about BFSP1 p.Leu72Pro (c.215T>C)?

AlphaMissense predicts likely pathogenic (score 0.823) — an in-silico prediction, not a clinical call.

BFSP1 p.Leu72Pro

c.215T>C · rs2123536475 · VCV1066273

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000286%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 33

Computational evidence

Protein change
AlphaMissense	0.823	likely pathogenic ✓ concordant with ClinVar · top 5% in BFSP1
REVEL	0.944	strongly pathogenic-leaning
SaProt	LLR -14.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	32.0	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 0.000286% European (non-Finnish) · 3/1,048,828 alleles

Filtering AF 7.6e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000253% 3/1,187,914 alleles · very rare

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.Leu72Pro
Coding: c.215T>C
MANE Select: NM_001195
dbSNP: rs2123536475
Type: single nucleotide variant
Location: chr20:17531115 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 72: the if rod domain; the 'coil 1a' 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-leu72pro (accessed [today's date]).

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