Is AP1G1 p.Val488Ile (c.1462G>A) pathogenic?

AP1G1 p.Val488Ile (c.1462G>A) is classified Likely benign in AP1G1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: likely benign (0.0709); Very rare (popmax 0.00167%, amr).

How common is AP1G1 p.Val488Ile (c.1462G>A) in the general population?

AP1G1 p.Val488Ile (c.1462G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AP1G1 p.Val488Ile (c.1462G>A)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

AP1G1 p.Val488Ile

c.1462G>A · VCV3911183

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.41	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 2.8	GERP -0.62, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.62 · regional, not allelic
Overall
CADD	19.55	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 0.00167% Admixed American · 1/60,018 alleles

Overall 6.84e-05% 1/1,461,008 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.Val488Ile
Coding: c.1462G>A
MANE Select: NM_001128
Type: single nucleotide variant
Location: chr16:71749929 (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.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
AP1G1 p.Ile769Val Uncertain significance ★★ ⚠ same type
AP1G1 c.2367+12A>G Benign ★★ same type
AP1G1 p.Thr179Ser Likely benign ★★ 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-val488ile (accessed [today's date]).

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