Is BFSP1 p.Leu302Val (c.904C>G) pathogenic?

BFSP1 p.Leu302Val (c.904C>G) is classified Uncertain significance in BFSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.3941); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BFSP1 p.Leu302Val (c.904C>G)?

BFSP1 p.Leu302Val (c.904C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BFSP1 p.Leu302Val (c.904C>G) in the general population?

BFSP1 p.Leu302Val (c.904C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BFSP1 p.Leu302Val (c.904C>G)?

AlphaMissense predicts ambiguous (score 0.3941) — an in-silico prediction, not a clinical call.

BFSP1 p.Leu302Val

c.904C>G · VCV4206524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3941	ambiguous
REVEL	0.724	pathogenic-leaning
SaProt	LLR -9.11	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.4 · regional, not allelic
Overall
CADD	23.5	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: BFSP1
Protein: p.Leu302Val
Coding: c.904C>G
MANE Select: NM_001195
Type: single nucleotide variant
Location: chr20:17498872 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.66
Residue 302: the if rod domain; the 'coil 2' region

Full BFSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Glu93Asp Uncertain significance ★★ ⚠ same condition
BFSP1 p.Ile631Asn Uncertain significance ★★ ⚠ same condition
BFSP1 p.Leu68Phe Uncertain significance ★★ same condition
BFSP1 p.Ser94Arg Uncertain significance ★★ ⚠ same condition
BFSP1 p.Thr490Ala Uncertain significance ★★ ⚠ same condition
BFSP1 p.Val480Leu 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-leu302val (accessed [today's date]).

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