Is AJAP1 p.Asp393Ala (c.1178A>C) pathogenic?

AJAP1 p.Asp393Ala (c.1178A>C) is classified Uncertain significance in AJAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely pathogenic (0.6215); Absent from gnomAD v4.1.

How common is AJAP1 p.Asp393Ala (c.1178A>C) in the general population?

AJAP1 p.Asp393Ala (c.1178A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AJAP1 p.Asp393Ala (c.1178A>C)?

AlphaMissense predicts likely pathogenic (score 0.6215) — an in-silico prediction, not a clinical call.

AJAP1 p.Asp393Ala

c.1178A>C · VCV3513207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6215 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6215	likely pathogenic
REVEL	0.442	indeterminate
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 119 kb · p 0.53 · regional, not allelic
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AJAP1
Protein: p.Asp393Ala
Coding: c.1178A>C
MANE Select: NM_018836
Type: single nucleotide variant
Location: chr1:4774441 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.22
Residue 393: the 'targeting signals' 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-asp393ala (accessed [today's date]).

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