Is BST1 p.Arg124His (c.371G>A) pathogenic?

BST1 p.Arg124His (c.371G>A) is classified Uncertain significance in BST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1003); Ultra-rare (popmax 0.015%, amr).

How common is BST1 p.Arg124His (c.371G>A) in the general population?

BST1 p.Arg124His (c.371G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about BST1 p.Arg124His (c.371G>A)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

BST1 p.Arg124His

c.371G>A · rs777458820 · VCV3135333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -5.89	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 0.15	GERP -2.5
Regional constraint	o/e 1.07	unconstrained · MANE · 29 kb · p 0.17 · regional, not allelic
Overall
CADD	14.47	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 0.015% Admixed American · 9/59,936 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.0013% 21/1,612,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,660
Remaining individualsnot grpmax-eligible	0.0032%	31,211
East Asian	0.00223%	44,780
South Asian	0.0011%	91,022
European (non-Finnish)	0.000678%	147,431

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.Arg124His
Coding: c.371G>A
MANE Select: NM_004334
dbSNP: rs777458820
Type: single nucleotide variant
Location: chr4:15707566 (GRCh38)
Gene constraint: LOEUF 1.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.33 · 6 PDB
Residue 124: a disulfide bond; a turn

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

Similar variants

BST1 p.Arg124Cys Benign ★ ⚠ 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-arg124his (accessed [today's date]).

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