Is SUOX p.Pro96= (c.288T>C) pathogenic?

SUOX p.Pro96= (c.288T>C) is classified Likely benign in SUOX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-17). Very rare (popmax 0.00133%, afr); Associated with isolated sulfite oxidase deficiency.

What condition is associated with SUOX p.Pro96= (c.288T>C)?

SUOX p.Pro96= (c.288T>C) is associated with isolated sulfite oxidase deficiency (ClinVar).

How common is SUOX p.Pro96= (c.288T>C) in the general population?

SUOX p.Pro96= (c.288T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

SUOX p.Pro96=

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.288T>C · rs764352363 · VCV1922671

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 0.047	GERP -2.8, phastCons 0.05
Overall
CADD	6.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,044 alleles

Overall 0.000248% 4/1,613,672 alleles · very rare exomes 4/1,461,352 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,831
African / African-Americangrpmax	0.00133%	75,044

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro96=
Coding: c.288T>C
MANE Select: NM_001032386
dbSNP: rs764352363
Type: single nucleotide variant
Location: chr12:56003677 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99 · 1 PDB
Residue 96: the cytochrome b5 heme-binding domain; a turn

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-pro96 (accessed [today's date]).

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