Is AP1G1 p.Pro471Ala (c.1411C>G) pathogenic?

AP1G1 p.Pro471Ala (c.1411C>G) is classified Uncertain significance in AP1G1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: ambiguous (0.3442); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AP1G1 p.Pro471Ala (c.1411C>G)?

AP1G1 p.Pro471Ala (c.1411C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AP1G1 p.Pro471Ala (c.1411C>G) in the general population?

AP1G1 p.Pro471Ala (c.1411C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about AP1G1 p.Pro471Ala (c.1411C>G)?

AlphaMissense predicts ambiguous (score 0.3442) — an in-silico prediction, not a clinical call.

AP1G1 p.Pro471Ala

c.1411C>G · rs369109806 · VCV2465492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3442	ambiguous
REVEL	0.204	benign-leaning
SaProt	LLR -9.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.62 · regional, not allelic
Overall
CADD	25.9	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 0.000424% European (non-Finnish) · 5/1,178,096 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,611,840 alleles · very rare exomes 5/1,459,598 · genomes 0/152,242 · joint denominator

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.Pro471Ala
Coding: c.1411C>G
MANE Select: NM_001128
dbSNP: rs369109806
Type: single nucleotide variant
Location: chr16:71749980 (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-pro471ala (accessed [today's date]).

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