Is SCO2 p.Ala93= (c.279C>T) pathogenic?

SCO2 p.Ala93= (c.279C>T) is classified Likely benign in SCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-16). Ultra-rare (popmax 0.0166%, mid).

How common is SCO2 p.Ala93= (c.279C>T) in the general population?

SCO2 p.Ala93= (c.279C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

SCO2 p.Ala93=

c.279C>T · VCV4731302

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

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 0.39	GERP -1.5, phastCons 0.83
Overall
CADD	7.219	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,038 alleles

Overall 6.85e-05% 1/1,460,152 alleles · ultra-rare

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.Ala93=
Coding: c.279C>T
MANE Select: NM_005138
Type: single nucleotide variant
Location: chr22:50524133 (GRCh38)
Gene constraint: LOEUF 1.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 1 PDB
Residue 93: the thioredoxin domain

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

Similar variants

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
SCO2 p.Gly242Arg 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-ala93 (accessed [today's date]).

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