Is CYBB p.Ser200Phe (c.599C>T) pathogenic?

CYBB p.Ser200Phe (c.599C>T) is classified Likely pathogenic in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-21). AlphaMissense: likely pathogenic (0.6452); Absent from gnomAD v4.1.

How common is CYBB p.Ser200Phe (c.599C>T) in the general population?

CYBB p.Ser200Phe (c.599C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Ser200Phe (c.599C>T)?

AlphaMissense predicts likely pathogenic (score 0.6452) — an in-silico prediction, not a clinical call.

CYBB p.Ser200Phe

c.599C>T · rs1556468360 · VCV450884

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6452 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6452	likely pathogenic ✓ concordant with ClinVar
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.62 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 0.00012 · regional, not allelic
Overall
CADD	26.5	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: CYBB
Protein: p.Ser200Phe
Coding: c.599C>T
MANE Select: NM_000397
dbSNP: rs1556468360
Type: single nucleotide variant
Location: chrX:37796066 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 200: an α-helix; the ferric oxidoreductase domain; a binding site

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

Similar variants

CYBB c.1151+2T>C Pathogenic ★★ same type
CYBB c.1315-2A>G Pathogenic/Likely pathogenic ★★ same type
CYBB c.141+1G>T Pathogenic ★★ same type
CYBB c.252+5G>A Pathogenic ★★ same type
CYBB c.483+1G>A Pathogenic ★★ same type
CYBB c.483+1G>T Pathogenic ★★ same type
CYBB c.483+3A>T Likely pathogenic ★★ same type
CYBB p.Ala156Thr Pathogenic/Likely pathogenic ★★ ⚠ same type

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/cybb-p-ser200phe (accessed [today's date]).

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