Is AP4E1 p.Asp300= (c.900T>C) pathogenic?

AP4E1 p.Asp300= (c.900T>C) is classified Likely benign in AP4E1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). Absent from gnomAD v4.1; Associated with Spastic paraplegia.

What condition is associated with AP4E1 p.Asp300= (c.900T>C)?

AP4E1 p.Asp300= (c.900T>C) is associated with Spastic paraplegia (ClinVar).

How common is AP4E1 p.Asp300= (c.900T>C) in the general population?

AP4E1 p.Asp300= (c.900T>C) is absent from gnomAD v4.1 (gnomAD).

AP4E1 p.Asp300=

c.900T>C · rs2141164775 · VCV1561401

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.51, phastCons 1
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

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: AP4E1
Protein: p.Asp300=
Coding: c.900T>C
MANE Select: NM_007347
dbSNP: rs2141164775
Type: single nucleotide variant
Location: chr15:50934654 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.42 · 4 PDB

Full AP4E1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP4E1 p.Asp300Val Uncertain significance ★ same residue
AP4E1 p.Arg304Ter Pathogenic/Likely pathogenic ★★ same condition
AP4E1 p.Ala119Ser Uncertain significance ★★ ⚠ same condition
AP4E1 p.Ala45Thr Uncertain significance ★★ ⚠ same condition
AP4E1 p.Ala475Val Uncertain significance ★★ ⚠ same condition
AP4E1 p.Arg646Cys Uncertain significance ★★ same condition
AP4E1 p.Asn1086Ser Uncertain significance ★★ ⚠ same condition
AP4E1 p.Asp484Val 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/ap4e1-p-asp300 (accessed [today's date]).

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