Is CYBB p.Asn22Ser (c.65A>G) pathogenic?

CYBB p.Asn22Ser (c.65A>G) is classified Uncertain significance in CYBB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely pathogenic (0.7617); Absent from gnomAD v4.1.

How common is CYBB p.Asn22Ser (c.65A>G) in the general population?

CYBB p.Asn22Ser (c.65A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Asn22Ser (c.65A>G)?

AlphaMissense predicts likely pathogenic (score 0.7617) — an in-silico prediction, not a clinical call.

CYBB p.Asn22Ser

c.65A>G · rs2146803116 · VCV1678088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7617 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7617	likely pathogenic
REVEL	0.771	pathogenic-leaning
SaProt	LLR -13.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 0.00012 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Asn22Ser
Coding: c.65A>G
MANE Select: NM_000397
dbSNP: rs2146803116
Type: single nucleotide variant
Location: chrX:37782107 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 22: an α-helix

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

Similar variants

CYBB p.Asn22= Likely benign ★★ same residue
CYBB p.Asn22Lys Uncertain significance ★ same residue
CYBB p.Asn22Tyr Uncertain significance ★ ⚠ same residue
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

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-asn22ser (accessed [today's date]).

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