Is SCO2 p.Arg120Pro (c.359G>C) pathogenic?

SCO2 p.Arg120Pro (c.359G>C) is classified Uncertain significance in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-06). AlphaMissense: ambiguous (0.3909); Very rare (popmax 0.00329%, sas).

How common is SCO2 p.Arg120Pro (c.359G>C) in the general population?

SCO2 p.Arg120Pro (c.359G>C) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about SCO2 p.Arg120Pro (c.359G>C)?

AlphaMissense predicts ambiguous (score 0.3909) — an in-silico prediction, not a clinical call.

SCO2 p.Arg120Pro

c.359G>C · rs768674109 · VCV1511650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3909	ambiguous
REVEL	0.701	pathogenic-leaning
SaProt	LLR -10.79	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.34	GERP -5.2
Regional constraint	o/e 1.23	unconstrained · MANE · 797 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	19.11	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 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,613,414 alleles · very rare exomes 4/1,461,094 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Admixed American	0.00167%	60,026

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.Arg120Pro
Coding: c.359G>C
MANE Select: NM_005138
dbSNP: rs768674109
Type: single nucleotide variant
Location: chr22:50524053 (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-arg120pro (accessed [today's date]).

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