Is BMS1 p.Arg863= (c.2589C>T) pathogenic?

BMS1 p.Arg863= (c.2589C>T) is classified Benign in BMS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.42%, mid).

How common is BMS1 p.Arg863= (c.2589C>T) in the general population?

BMS1 p.Arg863= (c.2589C>T) is low-frequency (popmax 1.42%, mid) (gnomAD).

BMS1 p.Arg863=

c.2589C>T · rs145515531 · VCV771884

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP -3.1
Overall
CADD	0.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% Middle Eastern · 86/6,056 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.897% 14,457/1,611,340 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.7%	27
Amishnot grpmax-eligible	2.85%	35
Middle Easterngrpmax	1.42%	70
Remaining individualsnot grpmax-eligible	1.23%	81
European (non-Finnish)	0.967%	103
Admixed American	0.748%	134
South Asian	0.497%	201
African / African-American	0.189%	528
Finnishnot grpmax-eligible	0.0454%	2,202
East Asian	0.00668%	14,959

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BMS1
Protein: p.Arg863=
Coding: c.2589C>T
MANE Select: NM_014753
dbSNP: rs145515531
Type: single nucleotide variant
Location: chr10:42820244 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 863: an α-helix

Full BMS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMS1 p.Arg863Cys Uncertain significance ★ ⚠ same residue
BMS1 p.Arg863His Uncertain significance ★ ⚠ same residue
BMS1 p.Ala214Val Benign/Likely benign ★★ same type
BMS1 p.Ala500= Benign/Likely benign ★★ same type
BMS1 p.Arg237His Benign ★★ same type
BMS1 p.Arg38Trp Benign/Likely benign ★★ ⚠ same type
BMS1 p.Asp768Asn Benign ★★ same type
BMS1 p.Glu1278= Likely benign ★★ 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/bms1-p-arg863 (accessed [today's date]).

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