Is CPB1 p.His64= (c.192C>T) pathogenic?

CPB1 p.His64= (c.192C>T) is classified Likely benign in CPB1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-08). Rare (popmax 0.188%, nfe); Associated with CPB1-related disorder.

What condition is associated with CPB1 p.His64= (c.192C>T)?

CPB1 p.His64= (c.192C>T) is associated with CPB1-related disorder (ClinVar).

How common is CPB1 p.His64= (c.192C>T) in the general population?

CPB1 p.His64= (c.192C>T) is rare (popmax 0.188%, nfe) (gnomAD).

CPB1 p.His64=

c.192C>T · rs146944241 · VCV3033459

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.188%, nfe)

Conditions

CPB1-related disorder

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 -1.7	GERP 0.51
Overall
CADD	2.711	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.188% European (non-Finnish) · 2,213/1,179,472 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.178%

Overall 0.15% 2,428/1,613,568 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.188%	533
Admixed American	0.125%	800
Remaining individualsnot grpmax-eligible	0.114%	880
South Asian	0.0593%	1,686
Middle Eastern	0.033%	3,029
African / African-American	0.0107%	9,381
Finnishnot grpmax-eligible	0.00625%	16,010
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596

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: CPB1
Protein: p.His64=
Coding: c.192C>T
MANE Select: NM_001871
dbSNP: rs146944241
Type: single nucleotide variant
Location: chr3:148834542 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.71 · 2 PDB
Residue 64: a β-strand

Full CPB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CPB1-related disorder

Similar variants

CPB1 p.Arg42His Benign ⚠ same condition
CPB1 p.Asp172Glu Benign ⚠ same condition
CPB1 p.Asp208Asn Benign ⚠ same condition
CPB1 p.Gly24= Benign same condition
CPB1 p.Phe232Leu Benign ⚠ same condition
CPB1 p.Ser65Gly Likely benign ⚠ same condition
CPB1 c.778+6T>C Benign ★★ same type
CPB1 p.Ile394Met 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/cpb1-p-his64 (accessed [today's date]).

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