Is AP3D1 p.Val1158Ile (c.3472G>A) pathogenic?

AP3D1 p.Val1158Ile (c.3472G>A) is classified Likely benign in AP3D1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.1003); Rare (popmax 0.183%, sas).

How common is AP3D1 p.Val1158Ile (c.3472G>A) in the general population?

AP3D1 p.Val1158Ile (c.3472G>A) is rare (popmax 0.183%, sas) (gnomAD).

What do computational predictors say about AP3D1 p.Val1158Ile (c.3472G>A)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

AP3D1 p.Val1158Ile

c.3472G>A · rs762878489 · VCV1580212

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.183%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 0.99, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 8,543 bp · p 0.28 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V1096I vs ClinVar V1158I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% South Asian · 165/90,090 alleles

Filtering AF 0.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.152%

Overall 0.0109% 176/1,608,040 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.183%	546
Remaining individualsnot grpmax-eligible	0.00643%	15,556
African / African-American	0.00268%	37,296
East Asian	0.00223%	44,776
Admixed American	0.00173%	57,858
European (non-Finnish)	0.000255%	392,759

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: AP3D1
Protein: p.Val1158Ile
Coding: c.3472G>A
MANE Select: NM_001261826
dbSNP: rs762878489
Type: single nucleotide variant
Location: chr19:2109086 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB

Full AP3D1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3D1 p.Val1158= Likely benign ★★ same residue
AP3D1 p.Val1158Leu Uncertain significance ★ ⚠ same residue
AP3D1 c.2001+6C>T Uncertain significance ★★ same type
AP3D1 c.2601+6G>T Uncertain significance ★★ same type
AP3D1 c.856+3G>A Uncertain significance ★★ same type
AP3D1 p.Ala1076Val Uncertain significance ★★ ⚠ same type
AP3D1 p.Ala1093Val Uncertain significance ★★ ⚠ same type
AP3D1 p.Ala1148Val 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/ap3d1-p-val1158ile (accessed [today's date]).

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