Is CYBB p.Ile273Val (c.817A>G) pathogenic?

CYBB p.Ile273Val (c.817A>G) is classified Conflicting classifications of pathogenicity in CYBB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-23). AlphaMissense: likely benign (0.1072); Ultra-rare (popmax 0.0132%, amr); Associated with Inborn genetic diseases.

What condition is associated with CYBB p.Ile273Val (c.817A>G)?

CYBB p.Ile273Val (c.817A>G) is associated with Inborn genetic diseases, granulomatous disease, chronic, X-linked (ClinVar).

How common is CYBB p.Ile273Val (c.817A>G) in the general population?

CYBB p.Ile273Val (c.817A>G) is ultra-rare (popmax 0.0132%, amr) (gnomAD).

What do computational predictors say about CYBB p.Ile273Val (c.817A>G)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

CYBB p.Ile273Val

c.817A>G · rs782610130 · VCV1093431

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -3.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.7, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 5,249 bp · p 0.15 · regional, not allelic
Overall
CADD	17.71	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 0.0132% Admixed American · 6/45,589 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00389%

Overall 0.000499% 6/1,202,485 alleles · ultra-rare

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: CYBB
Protein: p.Ile273Val
Coding: c.817A>G
MANE Select: NM_000397
dbSNP: rs782610130
Type: single nucleotide variant
Location: chrX:37801268 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 273: the ferric oxidoreductase domain; 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

Also linked: granulomatous disease, chronic, X-linked

Similar variants

CYBB c.1315-2A>G Pathogenic/Likely pathogenic ★★ same condition
CYBB c.141+1G>T Pathogenic ★★ same condition
CYBB c.252+5G>A Pathogenic ★★ same condition
CYBB c.483+1G>A Pathogenic ★★ same condition
CYBB c.483+1G>T Pathogenic ★★ same condition
CYBB c.483+3A>T Likely pathogenic ★★ same condition
CYBB p.Ala156Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CYBB p.Ala57Glu 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/cybb-p-ile273val (accessed [today's date]).

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