Is AJAP1 p.Glu190Lys (c.568G>A) pathogenic?

AJAP1 p.Glu190Lys (c.568G>A) is classified Uncertain significance in AJAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.2164); Very rare (popmax 0.00507%, amr).

How common is AJAP1 p.Glu190Lys (c.568G>A) in the general population?

AJAP1 p.Glu190Lys (c.568G>A) is very rare (popmax 0.00507%, amr) (gnomAD).

What do computational predictors say about AJAP1 p.Glu190Lys (c.568G>A)?

AlphaMissense predicts likely benign (score 0.2164) — an in-silico prediction, not a clinical call.

AJAP1 p.Glu190Lys

c.568G>A · rs764876909 · VCV2256850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00507%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2164	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.92	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 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 119 kb · p 0.53 · regional, not allelic
Overall
CADD	26.5	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 0.00507% Admixed American · 3/59,188 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000673%

Overall 0.000206% 3/1,454,590 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: AJAP1
Protein: p.Glu190Lys
Coding: c.568G>A
MANE Select: NM_018836
dbSNP: rs764876909
Type: single nucleotide variant
Location: chr1:4712438 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.22
Residue 190: the 'disordered' region

Full AJAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AJAP1 p.Pro228Arg Uncertain significance ★★ ⚠ same type
AJAP1 p.Ser260Gly Uncertain significance ★★ ⚠ same type
AJAP1 p.Ala35Val Benign ★★ same type
AJAP1 p.Gly202Asp Benign ★★ same type
AJAP1 p.Ala115Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala122Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala123Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala142Val 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/ajap1-p-glu190lys (accessed [today's date]).

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