Is AP3D1 p.Gln347His (c.1041G>T) pathogenic?

AP3D1 p.Gln347His (c.1041G>T) is classified Uncertain significance in AP3D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-19). AlphaMissense: ambiguous (0.3429); Absent from gnomAD v4.1.

How common is AP3D1 p.Gln347His (c.1041G>T) in the general population?

AP3D1 p.Gln347His (c.1041G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3D1 p.Gln347His (c.1041G>T)?

AlphaMissense predicts ambiguous (score 0.3429) — an in-silico prediction, not a clinical call.

AP3D1 p.Gln347His

c.1041G>T · rs2512175743 · VCV2831551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3429 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3429	ambiguous
REVEL	0.116	moderately benign-leaning
SaProt	LLR -10.60	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,612 bp · p 7.4e-05 · regional, not allelic
Overall
CADD	21.6	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

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: AP3D1
Protein: p.Gln347His
Coding: c.1041G>T
MANE Select: NM_001261826
dbSNP: rs2512175743
Type: single nucleotide variant
Location: chr19:2121794 (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 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
AP3D1 p.Ala1213Thr Uncertain significance ★★ ⚠ same type
AP3D1 p.Ala247Val 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-gln347his (accessed [today's date]).

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