Is TPSB2 p.Arg87Ser (c.261G>C) pathogenic?

TPSB2 p.Arg87Ser (c.261G>C) is classified Conflicting classifications of pathogenicity in TPSB2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-01). Rare (popmax 0.209%, amr).

How common is TPSB2 p.Arg87Ser (c.261G>C) in the general population?

TPSB2 p.Arg87Ser (c.261G>C) is rare (popmax 0.209%, amr) (gnomAD).

TPSB2 p.Arg87Ser

c.261G>C · rs769403251 · VCV2338143

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.209%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.335	indeterminate
Splicing
SpliceAI	Δ0.51	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP -2.3	GERP -2.5
Regional constraint	o/e 0.37	unconstrained · MANE · 123 bp · p 5.7e-05 · regional, not allelic
Overall
CADD	18.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.209% Admixed American · 58/27,798 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.189%

Overall 0.182% 2,274/1,251,464 alleles · rare exomes 2,149/1,183,002 · genomes 125/68,462 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.254%	394
Remaining individualsnot grpmax-eligible	0.225%	445
Admixed Americangrpmax	0.209%	479
European (non-Finnish)	0.199%	502
Ashkenazi Jewishnot grpmax-eligible	0.178%	561
African / African-American	0.0345%	2,895
Middle Eastern	0.0285%	3,514

Finnish 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: TPSB2
Protein: p.Arg87Ser
Coding: c.261G>C
MANE Select: NM_024164
dbSNP: rs769403251
Type: single nucleotide variant
Location: chr16:1229429 (GRCh38)
Gene constraint: LOEUF 1.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.79 · 13 PDB
Residue 87: a β-strand; the peptidase s1 domain

Full TPSB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TPSB2 p.Gly23Val Benign ★★ same type
TPSB2 p.Val76Leu Benign ★★ same type
TPSB2 p.Ala120Val Uncertain significance ★ same type
TPSB2 p.Ala123Thr Uncertain significance ★ same type
TPSB2 p.Ala16Ser Uncertain significance ★ same type
TPSB2 p.Ala21Val Uncertain significance ★ same type
TPSB2 p.Ala25Thr Uncertain significance ★ same type
TPSB2 p.Ala72Pro 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/tpsb2-p-arg87ser (accessed [today's date]).

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