Is CAAP1 p.Glu188Gly (c.563A>G) pathogenic?

CAAP1 p.Glu188Gly (c.563A>G) is classified Uncertain significance in CAAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.425); Very rare (popmax 0.000173%, nfe).

How common is CAAP1 p.Glu188Gly (c.563A>G) in the general population?

CAAP1 p.Glu188Gly (c.563A>G) is very rare (popmax 0.000173%, nfe) (gnomAD).

What do computational predictors say about CAAP1 p.Glu188Gly (c.563A>G)?

AlphaMissense predicts ambiguous (score 0.425) — an in-silico prediction, not a clinical call.

CAAP1 p.Glu188Gly

c.563A>G · VCV4217569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

Computational evidence

Protein change
AlphaMissense	0.425	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -10.84	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	27.5	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 0.000173% European (non-Finnish) · 2/1,155,792 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000142% 2/1,403,856 alleles · very rare

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: CAAP1
Protein: p.Glu188Gly
Coding: c.563A>G
MANE Select: NM_024828
Type: single nucleotide variant
Location: chr9:26886130 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.18

Full CAAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAAP1 p.Ala209Val Uncertain significance ★ ⚠ same type
CAAP1 p.Ala22Glu Uncertain significance ★ ⚠ same type
CAAP1 p.Ala261Gly Uncertain significance ★ ⚠ same type
CAAP1 p.Ala288Gly Uncertain significance ★ ⚠ same type
CAAP1 p.Ala322Ser Uncertain significance ★ ⚠ same type
CAAP1 p.Ala347Pro Uncertain significance ★ ⚠ same type
CAAP1 p.Ala354Pro Uncertain significance ★ ⚠ same type
CAAP1 p.Arg12Gly 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/caap1-p-glu188gly (accessed [today's date]).

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