Is BST1 p.Arg221= (c.663A>G) pathogenic?

BST1 p.Arg221= (c.663A>G) is classified Likely benign in BST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-29). Ultra-rare (popmax 0.0168%, nfe).

How common is BST1 p.Arg221= (c.663A>G) in the general population?

BST1 p.Arg221= (c.663A>G) is ultra-rare (popmax 0.0168%, nfe) (gnomAD).

BST1 p.Arg221=

c.663A>G · rs374610644 · VCV753442

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.041	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.069	GERP 0.55
Overall
CADD	6.998	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% European (non-Finnish) · 198/1,176,466 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0135% 216/1,601,324 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0168%	5,942
Remaining individualsnot grpmax-eligible	0.0161%	6,199
Admixed American	0.00709%	14,109
African / African-American	0.00538%	18,580

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.Arg221=
Coding: c.663A>G
MANE Select: NM_004334
dbSNP: rs374610644
Type: single nucleotide variant
Location: chr4:15715758 (GRCh38)
Gene constraint: LOEUF 1.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.33 · 6 PDB
Residue 221: a β-strand

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

Similar variants

BST1 p.Arg221Gln Uncertain significance ★ ⚠ same residue
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

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-arg221 (accessed [today's date]).

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