Is SUOX p.Arg76Ser (c.228G>T) pathogenic?

SUOX p.Arg76Ser (c.228G>T) is classified Conflicting classifications of pathogenicity in SUOX (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.154); Ultra-rare (popmax 0.099%, mid); Associated with isolated sulfite oxidase deficiency.

What condition is associated with SUOX p.Arg76Ser (c.228G>T)?

SUOX p.Arg76Ser (c.228G>T) is associated with isolated sulfite oxidase deficiency (ClinVar).

How common is SUOX p.Arg76Ser (c.228G>T) in the general population?

SUOX p.Arg76Ser (c.228G>T) is ultra-rare (popmax 0.099%, mid) (gnomAD).

What do computational predictors say about SUOX p.Arg76Ser (c.228G>T)?

AlphaMissense predicts likely benign (score 0.154) — an in-silico prediction, not a clinical call.

SUOX p.Arg76Ser

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.228G>T · rs202085145 · VCV309833

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.154 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

isolated sulfite oxidase deficiency

Computational evidence

Protein change
AlphaMissense	0.154	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.36	donor loss · deltas
Pangolin	Δ0.34	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.4	GERP 0.98, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,802 bp · p 0.031 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,058 alleles

Filtering AF 0.0708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0639%

Overall 0.0583% 941/1,613,944 alleles · ultra-rare exomes 853/1,461,740 · genomes 88/152,204 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.53%	65
Remaining individualsnot grpmax-eligible	0.157%	638
Middle Easterngrpmax	0.099%	1,010
Admixed American	0.09%	1,111
European (non-Finnish)	0.0277%	3,609
African / African-American	0.004%	25,002

Ashkenazi Jewish 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.Arg76Ser
Coding: c.228G>T
MANE Select: NM_001032386
dbSNP: rs202085145
Type: single nucleotide variant
Location: chr12:56002720 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99 · 1 PDB

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-arg76ser (accessed [today's date]).

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