Is SCO2 p.Val181= (c.543C>G) pathogenic?

SCO2 p.Val181= (c.543C>G) is classified Likely benign in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). Very rare (popmax 0.00167%, amr).

How common is SCO2 p.Val181= (c.543C>G) in the general population?

SCO2 p.Val181= (c.543C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

SCO2 p.Val181=

c.543C>G · rs1245488256 · VCV2806287

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

⚠ 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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.35	GERP -5.2, phastCons 0.087
Overall
CADD	0.698	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 6.2e-05% 1/1,613,956 alleles · very rare exomes 1/1,461,642 · genomes 0/152,314 · joint denominator

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.Val181=
Coding: c.543C>G
MANE Select: NM_005138
dbSNP: rs1245488256
Type: single nucleotide variant
Location: chr22:50523869 (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-val181 (accessed [today's date]).

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