Is CYBB p.Trp28Ser (c.83G>C) pathogenic?

CYBB p.Trp28Ser (c.83G>C) is classified Uncertain significance in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.2539); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CYBB p.Trp28Ser (c.83G>C)?

CYBB p.Trp28Ser (c.83G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CYBB p.Trp28Ser (c.83G>C) in the general population?

CYBB p.Trp28Ser (c.83G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Trp28Ser (c.83G>C)?

AlphaMissense predicts likely benign (score 0.2539) — an in-silico prediction, not a clinical call.

CYBB p.Trp28Ser

c.83G>C · rs782408392 · VCV3079294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2539	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.46	GERP -3.5
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 0.00012 · regional, not allelic
Overall
CADD	5.162	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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.Trp28Ser
Coding: c.83G>C
MANE Select: NM_000397
dbSNP: rs782408392
Type: single nucleotide variant
Location: chrX:37782125 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 28: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYBB p.Ala224Ser Uncertain significance ★★ ⚠ same condition
CYBB p.Asn128Lys Uncertain significance ★★ ⚠ same condition
CYBB p.Glu402Asp Uncertain significance ★★ ⚠ same condition
CYBB p.Gly166Asp Uncertain significance ★★ ⚠ same condition
CYBB p.His449Arg Uncertain significance ★★ ⚠ same condition
CYBB p.Ile221Thr Uncertain significance ★★ ⚠ same condition
CYBB p.Ser87Leu Uncertain significance ★★ ⚠ same condition
CYBB p.Thr242Arg Uncertain significance ★★ ⚠ 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/cybb-p-trp28ser (accessed [today's date]).

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