Is CYBB p.Tyr41Asp (c.121T>G) pathogenic?

CYBB p.Tyr41Asp (c.121T>G) is classified Likely pathogenic in CYBB (ClinVar, Single submitter, 2 submitters; last evaluated 2018-05-17). AlphaMissense: likely pathogenic (0.9699); Absent from gnomAD v4.1; Associated with CYBB-related disorders.

What condition is associated with CYBB p.Tyr41Asp (c.121T>G)?

CYBB p.Tyr41Asp (c.121T>G) is associated with CYBB-related disorders (ClinVar).

How common is CYBB p.Tyr41Asp (c.121T>G) in the general population?

CYBB p.Tyr41Asp (c.121T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYBB p.Tyr41Asp (c.121T>G)?

AlphaMissense predicts likely pathogenic (score 0.9699) — an in-silico prediction, not a clinical call.

CYBB p.Tyr41Asp

c.121T>G · rs151344453 · VCV68375

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9699 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CYBB-related disorders

Computational evidence

Protein change
AlphaMissense	0.9699	likely pathogenic ✓ concordant with ClinVar
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -16.31	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 7.9	GERP 0.45, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 0.00012 · regional, not allelic
Overall
CADD	23.9	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.Tyr41Asp
Coding: c.121T>G
MANE Select: NM_000397
dbSNP: rs151344453
Type: single nucleotide variant
Location: chrX:37782163 (GRCh38)
Structure: AlphaFold pLDDT 90.29 · 6 PDB
Residue 41: an α-helix; a UniProt-annotated variant site (in cgdx)

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

Disease context

CYBB-related disorders

Similar variants

CYBB p.Tyr41Ter Pathogenic ★ same residue
CYBB p.Tyr41= Likely benign ★ same residue
CYBB c.252+5G>A Pathogenic ★★ same condition
CYBB p.Ala156Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CYBB p.Ala84= Pathogenic ★★ same condition
CYBB p.Arg226Ter Pathogenic ★★ same condition
CYBB p.Arg290Ter Pathogenic ★★ same condition
CYBB p.Arg73Ter 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-tyr41asp (accessed [today's date]).

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