Is SCO2 p.Pro19Ser (c.55C>T) pathogenic?

SCO2 p.Pro19Ser (c.55C>T) is classified Uncertain significance in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-27). AlphaMissense: likely benign (0.0834); Very rare (popmax 0.00668%, eas).

How common is SCO2 p.Pro19Ser (c.55C>T) in the general population?

SCO2 p.Pro19Ser (c.55C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about SCO2 p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

SCO2 p.Pro19Ser

c.55C>T · rs1240764131 · VCV1495767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.22	GERP -1.9, phastCons 0.002
Regional constraint	o/e 1.23	unconstrained · MANE · 797 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	9.172	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

Grpmax group 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00025% 4/1,602,046 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
European (non-Finnish)	8.48e-05%	1,179,928

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: SCO2
Protein: p.Pro19Ser
Coding: c.55C>T
MANE Select: NM_152299 · reported on NM_005138
dbSNP: rs1240764131
Type: single nucleotide variant
Location: chr22:50524357 (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-pro19ser (accessed [today's date]).

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