Is CPB2 p.Leu6Phe (c.16C>T) pathogenic?

CPB2 p.Leu6Phe (c.16C>T) is classified Likely benign in CPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: likely benign (0.0576); Absent from gnomAD v4.1.

How common is CPB2 p.Leu6Phe (c.16C>T) in the general population?

CPB2 p.Leu6Phe (c.16C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPB2 p.Leu6Phe (c.16C>T)?

AlphaMissense predicts likely benign (score 0.0576) — an in-silico prediction, not a clinical call.

CPB2 p.Leu6Phe

c.16C>T · VCV3269145

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0576 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0576	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.27	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 0.31	GERP -4.5, phastCons 0.45
Regional constraint	o/e 0.83	unconstrained · MANE · 51 kb · p 0.00014 · regional, not allelic
Overall
CADD	1.347	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPB2
Protein: p.Leu6Phe
Coding: c.16C>T
MANE Select: NM_001872
Type: single nucleotide variant
Location: chr13:46104994 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.32 · 10 PDB

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

Similar variants

CPB2 p.Asp142= Benign ★★ same type
CPB2 p.Tyr245= Likely 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

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-leu6phe (accessed [today's date]).

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