Is BFSP2 p.Leu392Pro (c.1175T>C) pathogenic?

BFSP2 p.Leu392Pro (c.1175T>C) is classified Uncertain significance in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: ambiguous (0.4928); Absent from gnomAD v4.1.

How common is BFSP2 p.Leu392Pro (c.1175T>C) in the general population?

BFSP2 p.Leu392Pro (c.1175T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BFSP2 p.Leu392Pro (c.1175T>C)?

AlphaMissense predicts ambiguous (score 0.4928) — an in-silico prediction, not a clinical call.

BFSP2 p.Leu392Pro

c.1175T>C · VCV3260833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4928 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4928	ambiguous
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -13.01	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP 0.77, phastCons 0.71
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	23.3	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.Leu392Pro
Coding: c.1175T>C
MANE Select: NM_003571
Type: single nucleotide variant
Location: chr3:133472496 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 392: the if rod domain

Full BFSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BFSP2 p.Arg4Lys Uncertain significance ★★ ⚠ same type
BFSP2 p.Arg52Gln Uncertain significance ★★ ⚠ same type
BFSP2 p.Arg5Ter Uncertain significance ★★ same type
BFSP2 p.Arg72His Uncertain significance ★★ ⚠ same type
BFSP2 p.Glu141Ala Uncertain significance ★★ ⚠ same type
BFSP2 p.Glu228Gly Uncertain significance ★★ ⚠ same type
BFSP2 p.Glu289Asp Uncertain significance ★★ ⚠ same type
BFSP2 p.Gly79Ser Uncertain significance ★★ ⚠ same type

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-leu392pro (accessed [today's date]).

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