Is AP1G1 p.Pro595Ala (c.1783C>G) pathogenic?

AP1G1 p.Pro595Ala (c.1783C>G) is classified Uncertain significance in AP1G1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0715); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with AP1G1 p.Pro595Ala (c.1783C>G)?

AP1G1 p.Pro595Ala (c.1783C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AP1G1 p.Pro595Ala (c.1783C>G) in the general population?

AP1G1 p.Pro595Ala (c.1783C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about AP1G1 p.Pro595Ala (c.1783C>G)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

AP1G1 p.Pro595Ala

c.1783C>G · VCV3922056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -5.70	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.62 · regional, not allelic
Overall
CADD	24.3	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 0.00534% African / African-American · 4/74,900 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,008 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: AP1G1
Protein: p.Pro595Ala
Coding: c.1783C>G
MANE Select: NM_001128
Type: single nucleotide variant
Location: chr16:71745562 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP1G1 p.His575Asp Uncertain significance ★★ ⚠ same condition
AP1G1 p.Ile769Val Uncertain significance ★★ ⚠ same condition
AP1G1 p.Thr179Ser Likely benign ★★ same condition
AP1G1 p.Arg379Ter Pathogenic ★ same condition
AP1G1 p.Gln694Ter Pathogenic ★ same condition
AP1G1 p.Ala342Val Uncertain significance ★ ⚠ same condition
AP1G1 p.Ala365Val Uncertain significance ★ ⚠ same condition
AP1G1 p.Ala462Gly Uncertain significance ★ ⚠ same condition

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-pro595ala (accessed [today's date]).

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