Is CYBB p.Asn3Thr (c.8A>C) pathogenic?

CYBB p.Asn3Thr (c.8A>C) is classified Conflicting classifications of pathogenicity in CYBB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-29). AlphaMissense: likely benign (0.199); Ultra-rare (popmax 0.0119%, eas); Associated with Inborn genetic diseases.

What condition is associated with CYBB p.Asn3Thr (c.8A>C)?

CYBB p.Asn3Thr (c.8A>C) is associated with Inborn genetic diseases, granulomatous disease, chronic, X-linked, chronic granulomatous disease (ClinVar).

How common is CYBB p.Asn3Thr (c.8A>C) in the general population?

CYBB p.Asn3Thr (c.8A>C) is ultra-rare (popmax 0.0119%, eas) (gnomAD).

What do computational predictors say about CYBB p.Asn3Thr (c.8A>C)?

AlphaMissense predicts likely benign (score 0.199) — an in-silico prediction, not a clinical call.

CYBB p.Asn3Thr

c.8A>C · rs782014879 · VCV1022770

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.199 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.199	likely benign
REVEL	0.587	indeterminate
SaProt	LLR -6.58	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 9.1	GERP 0.69, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 0.00012 · regional, not allelic
Overall
CADD	22.0	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 0.0119% East Asian · 4/33,752 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.000414% 5/1,208,415 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0119%	8,438
South Asian	0.00176%	56,757

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.Asn3Thr
Coding: c.8A>C
MANE Select: NM_000397
dbSNP: rs782014879
Type: single nucleotide variant
Location: chrX:37780085 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB

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 chronic granulomatous disease

Similar variants

CYBB c.1151+2T>C Pathogenic ★★ same condition
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

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-asn3thr (accessed [today's date]).

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