Is SCO2 p.Arg84fs (c.250_251del) pathogenic?

SCO2 p.Arg84fs (c.250251del) is classified Pathogenic in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Very rare (popmax 0.00133%, afr).

How common is SCO2 p.Arg84fs (c.250_251del) in the general population?

SCO2 p.Arg84fs (c.250_251del) is very rare (popmax 0.00133%, afr) (gnomAD).

SCO2 p.Arg84fs

c.250_251del · rs1569521573 · VCV2967556

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.56	GERP -2.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,070 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,611,122 alleles · very rare exomes 3/1,458,758 · genomes 0/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,070
European (non-Finnish)	0.000169%	590,009

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.Arg84fs
Coding: c.250_251del
MANE Select: NM_005138
dbSNP: rs1569521573
Type: Microsatellite
Location: chr22:50524161 (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-arg84fs (accessed [today's date]).

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