Is BST1 p.Arg50Pro (c.149G>C) pathogenic?

BST1 p.Arg50Pro (c.149G>C) is classified Uncertain significance in BST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.9622); Ultra-rare (popmax 0.0763%, sas).

How common is BST1 p.Arg50Pro (c.149G>C) in the general population?

BST1 p.Arg50Pro (c.149G>C) is ultra-rare (popmax 0.0763%, sas) (gnomAD).

What do computational predictors say about BST1 p.Arg50Pro (c.149G>C)?

AlphaMissense predicts likely pathogenic (score 0.9622) — an in-silico prediction, not a clinical call.

BST1 p.Arg50Pro

c.149G>C · VCV3482689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9622 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0763%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9622	likely pathogenic · top 3% in BST1
REVEL	0.5	indeterminate
SaProt	LLR -16.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 29 kb · p 0.17 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0763% South Asian · 64/83,922 alleles

Filtering AF 0.0612% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0558%

Overall 0.00908% 139/1,531,196 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0763%	1,311
Remaining individualsnot grpmax-eligible	0.00838%	11,935
European (non-Finnish)	0.00603%	16,596
Finnishnot grpmax-eligible	0.00215%	46,546

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: BST1
Protein: p.Arg50Pro
Coding: c.149G>C
MANE Select: NM_004334
Type: single nucleotide variant
Location: chr4:15703293 (GRCh38)
Gene constraint: LOEUF 1.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.33 · 6 PDB
Residue 50: an α-helix

Full BST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BST1 p.Arg145= Benign ★★ same type
BST1 p.Gly239Arg Benign ★★ ⚠ same type
BST1 p.Ile101Val Benign ★★ same type
BST1 p.Ala120Thr Uncertain significance ★ ⚠ same type
BST1 p.Ala175Ser Uncertain significance ★ ⚠ same type
BST1 p.Ala175Thr Uncertain significance ★ ⚠ same type
BST1 p.Ala27Val Uncertain significance ★ ⚠ same type
BST1 p.Ala2Thr 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/bst1-p-arg50pro (accessed [today's date]).

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