Is AP3B2 p.Ala819Val (c.2456C>T) pathogenic?

AP3B2 p.Ala819Val (c.2456C>T) is classified Uncertain significance in AP3B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-31). AlphaMissense: likely benign (0.0627); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with AP3B2 p.Ala819Val (c.2456C>T)?

AP3B2 p.Ala819Val (c.2456C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B2 p.Ala819Val (c.2456C>T) in the general population?

AP3B2 p.Ala819Val (c.2456C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about AP3B2 p.Ala819Val (c.2456C>T)?

AlphaMissense predicts likely benign (score 0.0627) — an in-silico prediction, not a clinical call.

AP3B2 p.Ala819Val

c.2456C>T · rs998727894 · VCV1359230

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0627	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.4, phastCons 0.047
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	17.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A800V vs ClinVar A819V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,046 alleles

Overall 6.84e-05% 1/1,461,610 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: AP3B2
Protein: p.Ala819Val
Coding: c.2456C>T
MANE Select: NM_001278512
dbSNP: rs998727894
Type: single nucleotide variant
Location: chr15:82663601 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73

Full AP3B2 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

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AP3B2 p.Ala1098Asp Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala4Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala633Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala710Thr Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala71Thr Uncertain significance ★★ ⚠ same condition
AP3B2 p.Arg1025Trp 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/ap3b2-p-ala819val (accessed [today's date]).

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