Is CYBA p.Val47Gly (c.140T>G) pathogenic?

CYBA p.Val47Gly (c.140T>G) is classified Uncertain significance in CYBA (ClinVar, No assertion criteria, 2 submitters). AlphaMissense: likely benign (0.1955); Very rare (popmax 0.000424%, nfe).

How common is CYBA p.Val47Gly (c.140T>G) in the general population?

CYBA p.Val47Gly (c.140T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CYBA p.Val47Gly (c.140T>G)?

AlphaMissense predicts likely benign (score 0.1955) — an in-silico prediction, not a clinical call.

CYBA p.Val47Gly

c.140T>G · rs552648681 · VCV1175171

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1955	likely benign
REVEL	0.652	pathogenic-leaning
SaProt	LLR -8.62	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP -1.5, phastCons 0.32
Regional constraint	o/e 1.20	unconstrained · MANE · 7,657 bp · p 0.00077 · regional, not allelic
Overall
CADD	19.03	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 0.000424% European (non-Finnish) · 5/1,177,862 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000344% 5/1,453,838 alleles · very 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: CYBA
Protein: p.Val47Gly
Coding: c.140T>G
MANE Select: NM_000101
dbSNP: rs552648681
Type: single nucleotide variant
Location: chr16:88647164 (GRCh38)
Gene constraint: LOEUF 1.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28 · 7 PDB
Residue 47: an α-helix

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

Similar variants

CYBA p.Val47Met Uncertain significance ★★ ⚠ same residue
CYBA p.Val47= Likely benign ★ same residue
CYBA c.128+2T>C Likely pathogenic ★★ same type
CYBA c.204-2A>G Pathogenic/Likely pathogenic ★★ same type
CYBA c.287+1G>T Pathogenic/Likely pathogenic ★★ same type
CYBA c.287+2T>C Pathogenic/Likely pathogenic ★★ same type
CYBA c.288-1G>T Pathogenic/Likely pathogenic ★★ same type
CYBA c.369+1G>A 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-val47gly (accessed [today's date]).

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