Is SUOX p.Tyr330Cys (c.989A>G) pathogenic?

SUOX p.Tyr330Cys (c.989A>G) is classified Uncertain significance in SUOX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-17). AlphaMissense: likely pathogenic (0.863); Very rare (popmax 0.00167%, amr); Associated with isolated sulfite oxidase deficiency.

What condition is associated with SUOX p.Tyr330Cys (c.989A>G)?

SUOX p.Tyr330Cys (c.989A>G) is associated with isolated sulfite oxidase deficiency (ClinVar).

How common is SUOX p.Tyr330Cys (c.989A>G) in the general population?

SUOX p.Tyr330Cys (c.989A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about SUOX p.Tyr330Cys (c.989A>G)?

AlphaMissense predicts likely pathogenic (score 0.863) — an in-silico prediction, not a clinical call.

SUOX p.Tyr330Cys

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.989A>G · rs767860898 · VCV1393770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

isolated sulfite oxidase deficiency

Computational evidence

Protein change
AlphaMissense	0.863	likely pathogenic
REVEL	0.985	strongly pathogenic-leaning
SaProt	LLR -12.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,802 bp · p 0.031 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,920 alleles · very rare exomes 4/1,461,772 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
African / African-American	0.00134%	74,900
European (non-Finnish)	0.000254%	393,321

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.Tyr330Cys
Coding: c.989A>G
MANE Select: NM_001032386
dbSNP: rs767860898
Type: single nucleotide variant
Location: chr12:56004378 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99 · 1 PDB
Residue 330: 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-tyr330cys (accessed [today's date]).

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