Is AP1G1 p.Thr596Pro (c.1786A>C) pathogenic?

AP1G1 p.Thr596Pro (c.1786A>C) is classified Uncertain significance in AP1G1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.0763); Absent from gnomAD v4.1.

How common is AP1G1 p.Thr596Pro (c.1786A>C) in the general population?

AP1G1 p.Thr596Pro (c.1786A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP1G1 p.Thr596Pro (c.1786A>C)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

AP1G1 p.Thr596Pro

c.1786A>C · VCV4532720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.62 · regional, not allelic
Overall
CADD	21.2	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

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: AP1G1
Protein: p.Thr596Pro
Coding: c.1786A>C
MANE Select: NM_001128
Type: single nucleotide variant
Location: chr16:71745559 (GRCh38)
Gene constraint: LOEUF 0.113 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 1 PDB

Full AP1G1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1G1 p.Thr596Ser Uncertain significance ★ ⚠ same residue
AP1G1 p.Thr596Ala Likely benign ★ same residue
AP1G1 p.Thr596Ile Likely benign ★ same residue
AP1G1 p.Arg15Trp Likely pathogenic ★★ same type
AP1G1 p.Arg416Ter Pathogenic ★★ same type
AP1G1 p.Arg46Ter Uncertain significance ★★ same type
AP1G1 p.Gly120Val Uncertain significance ★★ ⚠ same type
AP1G1 p.His575Asp 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/ap1g1-p-thr596pro (accessed [today's date]).

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