Is AP3B2 p.Pro867Ser (c.2599C>T) pathogenic?

AP3B2 p.Pro867Ser (c.2599C>T) is classified Uncertain significance in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-26). AlphaMissense: likely benign (0.0893); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 48.

What condition is associated with AP3B2 p.Pro867Ser (c.2599C>T)?

AP3B2 p.Pro867Ser (c.2599C>T) is associated with developmental and epileptic encephalopathy, 48 (ClinVar).

How common is AP3B2 p.Pro867Ser (c.2599C>T) in the general population?

AP3B2 p.Pro867Ser (c.2599C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3B2 p.Pro867Ser (c.2599C>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

AP3B2 p.Pro867Ser

c.2599C>T · rs2151427966 · VCV1342635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,698)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 48

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	21.2	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 P848S vs ClinVar P867S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,698). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP3B2
Protein: p.Pro867Ser
Coding: c.2599C>T
MANE Select: NM_001278512
dbSNP: rs2151427966
Type: single nucleotide variant
Location: chr15:82663132 (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

developmental and epileptic encephalopathy, 48 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP3B2 p.Pro867Leu Uncertain significance ★★ ⚠ same residue
AP3B2 p.Pro867= Likely benign ★★ same residue
AP3B2 p.Arg977Ter Pathogenic ★★ same condition
AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same condition
AP3B2 c.1110+3G>C Uncertain significance ★★ same condition
AP3B2 p.Ala1098Asp Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala546Pro Uncertain significance ★★ ⚠ same condition
AP3B2 p.Arg977Gln 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-pro867ser (accessed [today's date]).

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