Is CCKAR p.Val365Ile (c.1093G>A) pathogenic?

CCKAR p.Val365Ile (c.1093G>A) is classified Benign in CCKAR (ClinVar, Single submitter, 2 submitters). AlphaMissense: likely benign (0.1027); Low-frequency (popmax 2.28%, afr).

How common is CCKAR p.Val365Ile (c.1093G>A) in the general population?

CCKAR p.Val365Ile (c.1093G>A) is low-frequency (popmax 2.28%, afr) (gnomAD).

What do computational predictors say about CCKAR p.Val365Ile (c.1093G>A)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

CCKAR p.Val365Ile

c.1093G>A · rs52795588 · VCV17530

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.28%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -5.58	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 6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 8,626 bp · p 0.69 · regional, not allelic
Overall
CADD	28.5	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 2.28% African / African-American · 1,713/75,022 alleles

Filtering AF 2.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.16%

Overall 0.124% 2,001/1,613,510 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.28%	44
Admixed American	0.202%	496
Remaining individualsnot grpmax-eligible	0.158%	631
Middle Eastern	0.0495%	2,020
South Asian	0.00989%	10,110
European (non-Finnish)	0.00475%	21,066

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: CCKAR
Protein: p.Val365Ile
Coding: c.1093G>A
MANE Select: NM_000730
dbSNP: rs52795588
Type: single nucleotide variant
Location: chr4:26481832 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.36 · 14 PDB
Residue 365: an α-helix

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

Similar variants

CCKAR p.Ala142Glu Uncertain significance ★ ⚠ same type
CCKAR p.Ala142Val Uncertain significance ★ ⚠ same type
CCKAR p.Ala193Thr Uncertain significance ★ ⚠ same type
CCKAR p.Ala332Thr Uncertain significance ★ ⚠ same type
CCKAR p.Ala341Thr Uncertain significance ★ ⚠ same type
CCKAR p.Arg150Pro Uncertain significance ★ ⚠ same type
CCKAR p.Arg197Cys Uncertain significance ★ ⚠ same type
CCKAR p.Arg297Gln 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/cckar-p-val365ile (accessed [today's date]).

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