Is AP3D1 p.Ala247Val (c.740C>T) pathogenic?

AP3D1 p.Ala247Val (c.740C>T) is classified Uncertain significance in AP3D1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.717); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AP3D1 p.Ala247Val (c.740C>T)?

AP3D1 p.Ala247Val (c.740C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP3D1 p.Ala247Val (c.740C>T) in the general population?

AP3D1 p.Ala247Val (c.740C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about AP3D1 p.Ala247Val (c.740C>T)?

AlphaMissense predicts likely pathogenic (score 0.717) — an in-silico prediction, not a clinical call.

AP3D1 p.Ala247Val

c.740C>T · rs761137640 · VCV2855981

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.717	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -4.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 28 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	26.4	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 0.00017% European (non-Finnish) · 2/1,175,630 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,451,164 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: AP3D1
Protein: p.Ala247Val
Coding: c.740C>T
MANE Select: NM_001261826
dbSNP: rs761137640
Type: single nucleotide variant
Location: chr19:2129156 (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

Disease context

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

Similar variants

AP3D1 c.856+3G>A Uncertain significance ★★ same condition
AP3D1 p.Ala1076Val Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala285Ser Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala438Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala450Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala461Val Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala546Thr 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/ap3d1-p-ala247val (accessed [today's date]).

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