Is SCO2 p.Pro233Ala (c.697C>G) pathogenic?

SCO2 p.Pro233Ala (c.697C>G) is classified Uncertain significance in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-26). AlphaMissense: ambiguous (0.376); Absent from gnomAD v4.1.

How common is SCO2 p.Pro233Ala (c.697C>G) in the general population?

SCO2 p.Pro233Ala (c.697C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCO2 p.Pro233Ala (c.697C>G)?

AlphaMissense predicts ambiguous (score 0.376) — an in-silico prediction, not a clinical call.

SCO2 p.Pro233Ala

c.697C>G · rs886043566 · VCV287092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.376 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.376	ambiguous
REVEL	0.709	pathogenic-leaning
SaProt	LLR -12.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 797 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	24.4	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: SCO2
Protein: p.Pro233Ala
Coding: c.697C>G
MANE Select: NM_152299 · reported on NM_005138
dbSNP: rs886043566
Type: single nucleotide variant
Location: chr22:50523715 (GRCh38)

Full SCO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/sco2-p-pro233ala (accessed [today's date]).

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