Is CYBA p.Arg139fs (c.415del) pathogenic?

CYBA p.Arg139fs (c.415del) is classified Pathogenic in CYBA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-14). Absent from gnomAD v4.1.

How common is CYBA p.Arg139fs (c.415del) in the general population?

CYBA p.Arg139fs (c.415del) is absent from gnomAD v4.1 (gnomAD).

CYBA p.Arg139fs

c.415del · rs1567607736 · VCV596212

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,535,148)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.051	GERP -3.3, phastCons 0.77

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,535,148). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CYBA
Protein: p.Arg139fs
Coding: c.415del
MANE Select: NM_000101
dbSNP: rs1567607736
Type: Deletion
Location: chr16:88643526 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 139: the 'disordered' region

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

Similar variants

CYBA p.Arg139Gly Uncertain significance ★ ⚠ same residue
CYBA p.Arg139Trp Uncertain significance ⚠ same residue
CYBA c.288-3_300del Likely pathogenic ★★ same type
CYBA p.Arg90fs Pathogenic/Likely pathogenic ★★ same type
CYBA p.Ile26fs Pathogenic/Likely pathogenic ★★ same type
CYBA p.Lys58fs Pathogenic ★★ same type
CYBA p.Val99fs Pathogenic/Likely pathogenic ★★ same type
CYBA c.203+102_404del Likely 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/cyba-p-arg139fs (accessed [today's date]).

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