Is BFSP2 p.Val283Ile (c.847G>A) pathogenic?

BFSP2 p.Val283Ile (c.847G>A) is classified Uncertain significance in BFSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: likely benign (0.0861); Ultra-rare (popmax 0.0201%, eas).

How common is BFSP2 p.Val283Ile (c.847G>A) in the general population?

BFSP2 p.Val283Ile (c.847G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about BFSP2 p.Val283Ile (c.847G>A)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

BFSP2 p.Val283Ile

c.847G>A · rs146257317 · VCV3133789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 75 kb · p 0.73 · regional, not allelic
Overall
CADD	14.23	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

Grpmax group 0.0201% East Asian · 9/44,874 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000867% 14/1,614,148 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
Admixed American	0.00333%	30,016
Remaining individualsnot grpmax-eligible	0.0016%	62,500
Finnishnot grpmax-eligible	0.00156%	64,034
European (non-Finnish)	8.47e-05%	1,180,011

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: BFSP2
Protein: p.Val283Ile
Coding: c.847G>A
MANE Select: NM_003571
dbSNP: rs146257317
Type: single nucleotide variant
Location: chr3:133450420 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.15
Residue 283: 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-val283ile (accessed [today's date]).

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