Is CCKBR p.Pro42Ser (c.124C>T) pathogenic?

CCKBR p.Pro42Ser (c.124C>T) is classified Uncertain significance in CCKBR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0738); Very rare (popmax 0.00233%, eas).

How common is CCKBR p.Pro42Ser (c.124C>T) in the general population?

CCKBR p.Pro42Ser (c.124C>T) is very rare (popmax 0.00233%, eas) (gnomAD).

What do computational predictors say about CCKBR p.Pro42Ser (c.124C>T)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

CCKBR p.Pro42Ser

c.124C>T · VCV4221902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00233%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.56	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 7.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 12 kb · p 0.16 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00233% East Asian · 1/42,838 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000431%

Overall 0.00094% 15/1,595,588 alleles · very rare exomes 13/1,443,556 · genomes 2/152,032 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00233%	42,838
African / African-American	0.00136%	73,320
South Asian	0.00112%	89,236
European (non-Finnish)	0.00102%	97,776

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: CCKBR
Protein: p.Pro42Ser
Coding: c.124C>T
MANE Select: NM_176875
Type: single nucleotide variant
Location: chr11:6260052 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.56 · 5 PDB

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

Similar variants

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CCKBR p.Ala19Thr Uncertain significance ★ ⚠ same type
CCKBR p.Ala26Thr Uncertain significance ★ ⚠ same type
CCKBR p.Ala415Thr Uncertain significance ★ ⚠ same type
CCKBR p.Ala62Thr Uncertain significance ★ ⚠ same type
CCKBR p.Ala97Thr 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/cckbr-p-pro42ser (accessed [today's date]).

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