Is APOO p.Ile117Thr (c.350T>C) pathogenic?

APOO p.Ile117Thr (c.350T>C) is classified Pathogenic in APOO (ClinVar, Single submitter, 2 submitters; last evaluated 2020-03-25). AlphaMissense: ambiguous (0.4149); Very rare (popmax 0.00112%, nfe); Associated with Cognitive impairment and autistic features.

What condition is associated with APOO p.Ile117Thr (c.350T>C)?

APOO p.Ile117Thr (c.350T>C) is associated with Cognitive impairment and autistic features, lactic acidosis (ClinVar).

How common is APOO p.Ile117Thr (c.350T>C) in the general population?

APOO p.Ile117Thr (c.350T>C) is very rare (popmax 0.00112%, nfe) (gnomAD).

What do computational predictors say about APOO p.Ile117Thr (c.350T>C)?

AlphaMissense predicts ambiguous (score 0.4149) — an in-silico prediction, not a clinical call.

APOO p.Ile117Thr

c.350T>C · rs1925449605 · VCV976657

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4149 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

Conditions

Cognitive impairment and autistic features

Computational evidence

Protein change
AlphaMissense	0.4149	ambiguous
REVEL	0.452	indeterminate
SaProt	LLR -10.29	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 67 kb · p 0.15 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.00112% European (non-Finnish) · 10/894,800 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000912% 10/1,096,646 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APOO
Protein: p.Ile117Thr
Coding: c.350T>C
MANE Select: NM_024122
dbSNP: rs1925449605
Type: single nucleotide variant
Location: chrX:23868631 (GRCh38)
Structure: AlphaFold pLDDT 74.34

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

Disease context

Cognitive impairment and autistic features

Also linked: lactic acidosis

Similar variants

APOO p.Ser15Cys Likely benign same condition
APOO p.Ser162= Likely benign same condition
APOO c.117+16T>C Benign ★★ same type
APOO p.Leu166Val Benign ★★ 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

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-ile117thr (accessed [today's date]).

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