CYTH4 p.Leu88=
c.262C>T · rs73887105 · VCV734144
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.61%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -0.46, phastCons 1 |
| Overall | ||
| CADD | 9.309 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.61%
African / African-American · 1,957/75,002 alleles
Filtering AF
2.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.47%
Overall
0.133%
2,150/1,613,914 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.61% | 38 |
| Remaining individualsnot grpmax-eligible | 0.165% | 607 |
| Admixed American | 0.105% | 953 |
| Middle Eastern | 0.033% | 3,029 |
| South Asian | 0.00878% | 11,385 |
| Finnishnot grpmax-eligible | 0.00156% | 64,018 |
| European (non-Finnish) | 0.00136% | 73,742 |
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
- CYTH4
- Protein
- p.Leu88=
- Coding
- c.262C>T
- MANE Select
- NM_013385
- dbSNP
- rs73887105
- Type
- single nucleotide variant
- Location
- chr22:37297591 (GRCh38)
- Gene constraint
- LOEUF 0.516 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 87.17
- Residue 88
- the sec7 domain
Similar variants
- CYTH4 p.Asn107His Benign ★★ ⚠ same type
- CYTH4 p.Met74Val Benign ★★ ⚠ same type
- CYTH4 p.Ala136Thr Uncertain significance ★ ⚠ same type
- CYTH4 p.Ala166Val Uncertain significance ★ ⚠ same type
- CYTH4 p.Ala9Glu Uncertain significance ★ ⚠ same type
- CYTH4 p.Arg205Gln Uncertain significance ★ ⚠ same type
- CYTH4 p.Arg212Cys Uncertain significance ★ ⚠ same type
- CYTH4 p.Arg218Cys 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/cyth4-p-leu88 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown