Is AP4E1 p.Ala270Val (c.809C>T) pathogenic?

AP4E1 p.Ala270Val (c.809C>T) is classified Uncertain significance in AP4E1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: ambiguous (0.5202); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AP4E1 p.Ala270Val (c.809C>T)?

AP4E1 p.Ala270Val (c.809C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AP4E1 p.Ala270Val (c.809C>T) in the general population?

AP4E1 p.Ala270Val (c.809C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP4E1 p.Ala270Val (c.809C>T)?

AlphaMissense predicts ambiguous (score 0.5202) — an in-silico prediction, not a clinical call.

AP4E1 p.Ala270Val

c.809C>T · VCV3301036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5202 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5202	ambiguous
REVEL	0.605	indeterminate
SaProt	LLR -7.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 94 kb · p 0.65 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

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: AP4E1
Protein: p.Ala270Val
Coding: c.809C>T
MANE Select: NM_007347
Type: single nucleotide variant
Location: chr15:50930911 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP4E1 p.Ala65Val Uncertain significance ★★ ⚠ same condition
AP4E1 p.Ala678Val Uncertain significance ★★ ⚠ same condition
AP4E1 p.Arg304Gln Uncertain significance ★★ ⚠ same condition
AP4E1 p.Asp218Gly Uncertain significance ★★ ⚠ same condition
AP4E1 p.Gln1093Glu Uncertain significance ★★ ⚠ same condition
AP4E1 p.Gln375Pro Uncertain significance ★★ ⚠ same condition
AP4E1 p.Gln989Arg Uncertain significance ★★ ⚠ same condition
AP4E1 p.Gln993His 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-ala270val (accessed [today's date]).

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