Is BST1 p.Ile101Val (c.301A>G) pathogenic?

BST1 p.Ile101Val (c.301A>G) is classified Benign in BST1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.127); Common (popmax 9.71%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BST1 p.Ile101Val (c.301A>G)?

AlphaMissense predicts likely benign (score 0.127) — an in-silico prediction, not a clinical call.

BST1 p.Ile101Val

Q: How common is BST1 p.Ile101Val (c.301A>G) in the general population?

BST1 p.Ile101Val (c.301A>G) is common (popmax 9.71%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.301A>G · rs6840615 · VCV769628

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.127 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.71%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.127	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -4.47	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 1.9	GERP -1.9, phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 29 kb · p 0.17 · regional, not allelic
Overall
CADD	10.45	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

Grpmax group 9.71% African / African-American · 7,278/74,940 alleles

Filtering AF 9.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.45%

Overall 0.52% 8,399/1,613,918 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.71%	10
Middle Eastern	0.924%	108
Remaining individualsnot grpmax-eligible	0.658%	152
Admixed American	0.65%	154
South Asian	0.022%	4,554
European (non-Finnish)	0.0206%	4,856
East Asian	0.00223%	44,858

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.Ile101Val
Coding: c.301A>G
MANE Select: NM_004334
dbSNP: rs6840615
Type: single nucleotide variant
Location: chr4:15705627 (GRCh38)
Gene constraint: LOEUF 1.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.33 · 6 PDB
Residue 101: a disulfide bond; a UniProt-annotated variant site (in)

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.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
BST1 p.Ala30Thr 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-ile101val (accessed [today's date]).

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