Is APOO p.Pro30Leu (c.89C>T) pathogenic?

APOO p.Pro30Leu (c.89C>T) is classified Uncertain significance in APOO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0699); Absent from gnomAD v4.1.

How common is APOO p.Pro30Leu (c.89C>T) in the general population?

APOO p.Pro30Leu (c.89C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOO p.Pro30Leu (c.89C>T)?

AlphaMissense predicts likely benign (score 0.0699) — an in-silico prediction, not a clinical call.

APOO p.Pro30Leu

c.89C>T · VCV4127895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0699 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,188,141)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0699	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.78, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 67 kb · p 0.15 · regional, not allelic
Overall
CADD	19.59	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

No allele count reported in gnomAD v4.1 (AN 1,188,141). 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: APOO
Protein: p.Pro30Leu
Coding: c.89C>T
MANE Select: NM_024122
Type: single nucleotide variant
Location: chrX:23880873 (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-pro30leu (accessed [today's date]).

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