Is AP3B1 p.Pro370Ser (c.1108C>T) pathogenic?

AP3B1 p.Pro370Ser (c.1108C>T) is classified Uncertain significance in AP3B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.2621); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AP3B1 p.Pro370Ser (c.1108C>T)?

AP3B1 p.Pro370Ser (c.1108C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B1 p.Pro370Ser (c.1108C>T) in the general population?

AP3B1 p.Pro370Ser (c.1108C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3B1 p.Pro370Ser (c.1108C>T)?

AlphaMissense predicts likely benign (score 0.2621) — an in-silico prediction, not a clinical call.

AP3B1 p.Pro370Ser

c.1108C>T · VCV4115079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2621 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2621	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -9.40	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 10	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 213 kb · p 0.0039 · regional, not allelic
Overall
CADD	27.4	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.

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: AP3B1
Protein: p.Pro370Ser
Coding: c.1108C>T
MANE Select: NM_003664
Type: single nucleotide variant
Location: chr5:78175685 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.85 · 5 PDB

Full AP3B1 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

AP3B1 p.Ala643Val Uncertain significance ★★ ⚠ same condition
AP3B1 p.Ala844Val Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg227His Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg509Gln Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg649Gln Uncertain significance ★★ ⚠ same condition
AP3B1 p.Arg730Gln Uncertain significance ★★ ⚠ same condition
AP3B1 p.Asp285Gly Uncertain significance ★★ ⚠ same condition
AP3B1 p.Asp488Asn 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/ap3b1-p-pro370ser (accessed [today's date]).

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