Is APOO p.Ser15Cys (c.43A>T) pathogenic?

APOO p.Ser15Cys (c.43A>T) is classified Likely benign in APOO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.1181); Rare (popmax 0.461%, amr); Associated with APOO-related disorder.

What condition is associated with APOO p.Ser15Cys (c.43A>T)?

APOO p.Ser15Cys (c.43A>T) is associated with APOO-related disorder (ClinVar).

How common is APOO p.Ser15Cys (c.43A>T) in the general population?

APOO p.Ser15Cys (c.43A>T) is rare (popmax 0.461%, amr) (gnomAD).

What do computational predictors say about APOO p.Ser15Cys (c.43A>T)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

APOO p.Ser15Cys

c.43A>T · rs200861085 · VCV3053567

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.461%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

APOO-related disorder

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -7.27	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 3.4	GERP 0.38, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 67 kb · p 0.15 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.461% Admixed American · 193/41,888 alleles

Filtering AF 0.407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.387%

Overall 0.0178% 211/1,187,332 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.461%	217
African / African-American	0.0178%	5,609
Remaining individualsnot grpmax-eligible	0.0151%	6,643
European (non-Finnish)	0.000113%	885,747

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.Ser15Cys
Coding: c.43A>T
MANE Select: NM_024122
dbSNP: rs200861085
Type: single nucleotide variant
Location: chrX:23880919 (GRCh38)
Structure: AlphaFold pLDDT 74.34

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

Disease context

APOO-related disorder

Similar variants

APOO p.Ile117Thr Pathogenic ★ ⚠ 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-ser15cys (accessed [today's date]).

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