Is CCK p.Arg35Gln (c.104G>A) pathogenic?

CCK p.Arg35Gln (c.104G>A) is classified Likely benign in CCK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.0654); Very rare (popmax 0.00822%, nfe).

How common is CCK p.Arg35Gln (c.104G>A) in the general population?

CCK p.Arg35Gln (c.104G>A) is very rare (popmax 0.00822%, nfe) (gnomAD).

What do computational predictors say about CCK p.Arg35Gln (c.104G>A)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

CCK p.Arg35Gln

c.104G>A · rs758894615 · VCV2239220

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.29	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 -1.6	GERP -3.3
Regional constraint	o/e 0.86	unconstrained · MANE · 5,529 bp · p 0.07 · regional, not allelic
Overall
CADD	3.183	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

Grpmax group 0.00822% European (non-Finnish) · 97/1,179,684 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00638% 103/1,613,232 alleles · very rare exomes 95/1,460,988 · genomes 8/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,162
Remaining individualsnot grpmax-eligible	0.00641%	15,612
Finnishnot grpmax-eligible	0.00157%	63,684
African / African-American	0.00133%	74,930

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.Arg35Gln
Coding: c.104G>A
MANE Select: NM_000729
dbSNP: rs758894615
Type: single nucleotide variant
Location: chr3:42263527 (GRCh38)
Gene constraint: LOEUF 1.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.72 · 9 PDB
Residue 35: the 'disordered' region

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-arg35gln (accessed [today's date]).

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