GPATCH4 p.His22Tyr
c.64C>T · rs745392006 · VCV2232333
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00992%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.236 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.22 | donor gain, 2 bp away · raw score · deltas |
| Pangolin | Δ0.30 | gain · loss 0.11 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | GERP 2.6, phastCons 1 |
| Overall | ||
| CADD | 24.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00992%
European (non-Finnish) · 117/1,179,948 alleles
Filtering AF
0.00842%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00787%
Overall
0.0075%
121/1,613,926 alleles · very rare
exomes 110/1,461,746 · genomes 11/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00992% | 10,085 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| African / African-American | 0.00133% | 74,908 |
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
- GPATCH4
- Protein
- p.His22Tyr
- Coding
- c.64C>T
- dbSNP
- rs745392006
- Type
- single nucleotide variant
- Location
- chr1:156598983 (GRCh38)
- Gene constraint
- LOEUF 1.669 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 57.52
- Residue 22
- the g-patch domain
Similar variants
- GPATCH4 c.348+115G>A Uncertain significance ★ same type
- GPATCH4 c.-65A>C Uncertain significance ★ same type
- GPATCH4 c.-74G>C Uncertain significance ★ same type
- GPATCH4 c.-79G>C Uncertain significance ★ same type
- GPATCH4 p.Ala162Thr Uncertain significance ★ same type
- GPATCH4 p.Ala174Pro Uncertain significance ★ same type
- GPATCH4 p.Ala219Val Uncertain significance ★ same type
- GPATCH4 p.Ala316Val Uncertain significance ★ 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/gpatch4-p-his22tyr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown