Is SUOX p.Ser416Phe (c.1247C>T) pathogenic?

SUOX p.Ser416Phe (c.1247C>T) is classified Uncertain significance in SUOX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1603); Absent from gnomAD v4.1; Associated with isolated sulfite oxidase deficiency.

What condition is associated with SUOX p.Ser416Phe (c.1247C>T)?

SUOX p.Ser416Phe (c.1247C>T) is associated with isolated sulfite oxidase deficiency (ClinVar).

How common is SUOX p.Ser416Phe (c.1247C>T) in the general population?

SUOX p.Ser416Phe (c.1247C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SUOX p.Ser416Phe (c.1247C>T)?

AlphaMissense predicts likely benign (score 0.1603) — an in-silico prediction, not a clinical call.

SUOX p.Ser416Phe

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.1247C>T · rs886049683 · VCV309841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1603 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

isolated sulfite oxidase deficiency

Computational evidence

Protein change
AlphaMissense	0.1603	likely benign
REVEL	0.506	indeterminate
SaProt	LLR -12.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,802 bp · p 0.031 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SUOX
Protein: p.Ser416Phe
Coding: c.1247C>T
MANE Select: NM_001032386
dbSNP: rs886049683
Type: single nucleotide variant
Location: chr12:56004636 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99 · 1 PDB
Residue 416: the 'homodimerization' 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-ser416phe (accessed [today's date]).

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