Is SCO2 p.Ser251= (c.753A>G) pathogenic?

SCO2 p.Ser251= (c.753A>G) is classified Likely benign in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-22). Absent from gnomAD v4.1.

How common is SCO2 p.Ser251= (c.753A>G) in the general population?

SCO2 p.Ser251= (c.753A>G) is absent from gnomAD v4.1 (gnomAD).

SCO2 p.Ser251=

c.753A>G · rs2148670719 · VCV2831032

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -4
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

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.Ser251=
Coding: c.753A>G
MANE Select: NM_005138
dbSNP: rs2148670719
Type: single nucleotide variant
Location: chr22:50523659 (GRCh38)
Gene constraint: LOEUF 1.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 1 PDB
Residue 251: an α-helix; the thioredoxin domain

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

Similar variants

SCO2 p.Ser251delinsGlyTer Likely pathogenic ★ same residue
SCO2 p.Ala74Asp Uncertain significance ★★ ⚠ same type
SCO2 p.Arg120Trp Uncertain significance ★★ ⚠ same type
SCO2 p.Arg206Cys Uncertain significance ★★ ⚠ same type
SCO2 p.Arg206His Uncertain significance ★★ ⚠ same type
SCO2 p.Arg255Gln Uncertain significance ★★ ⚠ same type
SCO2 p.Arg95His Uncertain significance ★★ ⚠ same type
SCO2 p.Gly129Asp Uncertain significance ★★ ⚠ same type

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-ser251 (accessed [today's date]).

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