Is CPB2 p.Tyr245= (c.735T>C) pathogenic?

CPB2 p.Tyr245= (c.735T>C) is classified Likely benign in CPB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-04). Rare (popmax 0.709%, mid).

How common is CPB2 p.Tyr245= (c.735T>C) in the general population?

CPB2 p.Tyr245= (c.735T>C) is rare (popmax 0.709%, mid) (gnomAD).

CPB2 p.Tyr245=

c.735T>C · rs145262149 · VCV713135

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.709%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor gain, 32 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.34	GERP -3.6, phastCons 0.002
Overall
CADD	1.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.709% Middle Eastern · 43/6,062 alleles

Filtering AF 0.541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.482%

Overall 0.129% 2,090/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.98%	51
Middle Easterngrpmax	0.709%	141
Remaining individualsnot grpmax-eligible	0.23%	434
European (non-Finnish)	0.103%	974
Admixed American	0.0916%	1,092
Finnishnot grpmax-eligible	0.0562%	1,779
African / African-American	0.02%	5,005
South Asian	0.0011%	91,086

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: CPB2
Protein: p.Tyr245=
Coding: c.735T>C
MANE Select: NM_001872
dbSNP: rs145262149
Type: single nucleotide variant
Location: chr13:46064709 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.32 · 10 PDB
Residue 245: the peptidase m14 domain

Full CPB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPB2 p.Asp142= Benign ★★ same type
CPB2 p.Ala22Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala246Val Uncertain significance ★ ⚠ same type
CPB2 p.Ala340Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala411Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala74Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala7Glu Uncertain significance ★ ⚠ same type
CPB2 p.Arg342Cys 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/cpb2-p-tyr245 (accessed [today's date]).

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