CTLA4 p.Pro137=
c.411G>A · rs188862082 · VCV794310
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.3 | GERP -3 |
| Overall | ||
| CADD | 1.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0172% | 5,821 |
| African / African-Americangrpmax | 0.012% | 8,339 |
| Admixed American | 0.00333% | 30,012 |
| South Asian | 0.00329% | 30,361 |
| East Asian | 0.00223% | 44,882 |
| European (non-Finnish) | 0.00153% | 65,556 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- CTLA4
- Protein
- p.Pro137=
- Coding
- c.411G>A
- MANE Select
- NM_005214
- dbSNP
- rs188862082
- Type
- single nucleotide variant
- Location
- chr2:203870887 (GRCh38)
- Gene constraint
- LOEUF 0.211 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.67 · 22 PDB
- Residue 137
- a β-strand; the ig-like v-type domain; the 'important for interaction with cd80 and cd86' region
Disease context
autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adolescent, Adult, Childhood
Similar variants
- CTLA4 p.Pro137Arg Likely pathogenic ★★★ same residue
- CTLA4 p.Pro137Leu Likely pathogenic ★★★ same residue
- CTLA4 p.Pro137Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- CTLA4 p.Arg51Ter Pathogenic ★★★ same condition
- CTLA4 p.Arg75Trp Pathogenic ★★★ ⚠ same condition
- CTLA4 p.Asp153Asn Pathogenic ★★★ ⚠ same condition
- CTLA4 p.Cys35Ter Pathogenic ★★★ same condition
- CTLA4 p.Pro136Ala Likely 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/ctla4-p-pro137 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown