Is SUOX p.Asp228= (c.684C>T) pathogenic?

SUOX p.Asp228= (c.684C>T) is classified Likely benign in SUOX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). Very rare (popmax 0.00133%, afr); Associated with isolated sulfite oxidase deficiency.

What condition is associated with SUOX p.Asp228= (c.684C>T)?

SUOX p.Asp228= (c.684C>T) is associated with isolated sulfite oxidase deficiency (ClinVar).

How common is SUOX p.Asp228= (c.684C>T) in the general population?

SUOX p.Asp228= (c.684C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

SUOX p.Asp228=

Q: How is Encephalopathy due to sulfite oxidase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.684C>T · rs975895329 · VCV1558749

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

isolated sulfite oxidase deficiency

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 -0.85	GERP -4.7, phastCons 0.002
Overall
CADD	1.641	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Overall 0.000124% 2/1,614,052 alleles · very rare exomes 1/1,461,894 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,914
European (non-Finnish)	8.47e-05%	1,180,038

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: SUOX
Protein: p.Asp228=
Coding: c.684C>T
MANE Select: NM_001032386
dbSNP: rs975895329
Type: single nucleotide variant
Location: chr12:56004073 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99 · 1 PDB
Residue 228: the 'moco domain' region

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

Disease context

isolated sulfite oxidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Encephalopathy due to sulfite oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

SUOX c.228+1G>A Pathogenic/Likely pathogenic ★★ same condition
SUOX c.51-2A>C Likely pathogenic ★★ same condition
SUOX p.Arg217Gln Pathogenic/Likely pathogenic ★★ same condition
SUOX p.Arg366His Pathogenic/Likely pathogenic ★★ same condition
SUOX p.Arg459Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
SUOX p.Asp512Tyr Likely pathogenic ★★ same condition
SUOX p.Gln426Ter Pathogenic/Likely pathogenic ★★ same condition
SUOX p.Gly362Ser Pathogenic/Likely pathogenic ★★ same condition

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/suox-p-asp228 (accessed [today's date]).

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