Is AP3B2 p.Arg878Trp (c.2632C>T) pathogenic?

AP3B2 p.Arg878Trp (c.2632C>T) is classified Uncertain significance in AP3B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-01). AlphaMissense: likely benign (0.1058); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with AP3B2 p.Arg878Trp (c.2632C>T)?

AP3B2 p.Arg878Trp (c.2632C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B2 p.Arg878Trp (c.2632C>T) in the general population?

AP3B2 p.Arg878Trp (c.2632C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about AP3B2 p.Arg878Trp (c.2632C>T)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

AP3B2 p.Arg878Trp

c.2632C>T · rs201234574 · VCV1381315

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -12.01	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.1	GERP -3.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	25.3	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 R859W vs ClinVar R878W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,902 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0049% 79/1,612,990 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0832%	1,202
African / African-Americangrpmax	0.00534%	18,726
Remaining individualsnot grpmax-eligible	0.0032%	31,218
South Asian	0.0022%	45,482
Admixed American	0.00167%	59,884
European (non-Finnish)	0.00144%	69,394

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg878Trp
Coding: c.2632C>T
MANE Select: NM_001278512
dbSNP: rs201234574
Type: single nucleotide variant
Location: chr15:82662895 (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

AP3B2 p.Arg878Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AP3B2 c.2834-3C>A Uncertain significance ★★ same condition
AP3B2 p.Ala1076Pro Uncertain significance ★★ ⚠ same condition
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

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-arg878trp (accessed [today's date]).

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