Is APOO p.Tyr174His (c.520T>C) pathogenic?

APOO p.Tyr174His (c.520T>C) is classified Uncertain significance in APOO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely pathogenic (0.73); Absent from gnomAD v4.1.

How common is APOO p.Tyr174His (c.520T>C) in the general population?

APOO p.Tyr174His (c.520T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOO p.Tyr174His (c.520T>C)?

AlphaMissense predicts likely pathogenic (score 0.73) — an in-silico prediction, not a clinical call.

APOO p.Tyr174His

c.520T>C · VCV3418414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.73 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.73	likely pathogenic
REVEL	0.256	benign-leaning
SaProt	LLR -12.33	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.99, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 67 kb · p 0.15 · regional, not allelic
Overall
CADD	22.3	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: APOO
Protein: p.Tyr174His
Coding: c.520T>C
MANE Select: NM_024122
Type: single nucleotide variant
Location: chrX:23856343 (GRCh38)
Structure: AlphaFold pLDDT 74.34

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

Similar variants

APOO c.117+16T>C Benign ★★ same type
APOO p.Leu166Val Benign ★★ same type
APOO p.Ile117Thr Pathogenic ★ ⚠ same type
APOO p.Ala12Gly Uncertain significance ★ ⚠ same type
APOO p.Asp98Glu Uncertain significance ★ ⚠ same type
APOO p.Glu72Lys Uncertain significance ★ ⚠ same type
APOO p.Gly163Ala Uncertain significance ★ ⚠ same type
APOO p.Gly173Glu Uncertain significance ★ ⚠ same type

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/apoo-p-tyr174his (accessed [today's date]).

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