Is CCK p.Val5Ala (c.14T>C) pathogenic?

CCK p.Val5Ala (c.14T>C) is classified Uncertain significance in CCK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1112); Very rare (popmax 0.00338%, sas).

How common is CCK p.Val5Ala (c.14T>C) in the general population?

CCK p.Val5Ala (c.14T>C) is very rare (popmax 0.00338%, sas) (gnomAD).

What do computational predictors say about CCK p.Val5Ala (c.14T>C)?

AlphaMissense predicts likely benign (score 0.1112) — an in-silico prediction, not a clinical call.

CCK p.Val5Ala

c.14T>C · rs541463179 · VCV3139684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00338%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1112	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.50	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 4.3	GERP 0.59, phastCons 0.96
Regional constraint	o/e 0.86	unconstrained · MANE · 5,529 bp · p 0.07 · regional, not allelic
Overall
CADD	17.05	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 0.00338% South Asian · 3/88,746 alleles

Filtering AF 0.000898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000449%

Overall 0.00025% 4/1,598,668 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00338%	29,582
African / African-American	0.00134%	74,644

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: CCK
Protein: p.Val5Ala
Coding: c.14T>C
MANE Select: NM_000729
dbSNP: rs541463179
Type: single nucleotide variant
Location: chr3:42263617 (GRCh38)
Gene constraint: LOEUF 1.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.72 · 9 PDB

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

Similar variants

CCK p.Arg106Cys Uncertain significance ★ ⚠ same type
CCK p.Arg106His Uncertain significance ★ ⚠ same type
CCK p.Arg70Gly Uncertain significance ★ ⚠ same type
CCK p.Arg76Gln Uncertain significance ★ ⚠ same type
CCK p.Arg95Gln Uncertain significance ★ ⚠ same type
CCK p.Glu109Lys Uncertain significance ★ ⚠ same type
CCK p.Gly104Ala Uncertain significance ★ ⚠ same type
CCK p.Ser115Ala 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/cck-p-val5ala (accessed [today's date]).

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