CTLA4 p.Pro205=
c.615C>G · rs74808460 · VCV741101
ClinGen expert panel — Antibody Deficiencies VCEP
Benign for autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency. Applied ACMG criteria (verbatim):
BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
NM_005214.5(CTLA4):c.615C>G (p.Pro205=) is a synonymous variant in exon 2 that does not have a predicted impact at splicing sites (BP7). The splicing impact predictor SpliceAI gives a delta score of 0.03 for acceptor gain, which is below the ClinGen Antibody Deficiencies VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4). This variant is present in gnomAD v4.1.0 at a GrpMax allele frequency of 0.0004811, with 30 alleles / 44,874 total alleles in the East Asian population, which is higher than the ClinGen Antibody Deficiencies VCEP BA1 threshold of >0.0000111 (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Antibody Deficiencies VCEP: BA1, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 09/18/2025).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.079 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP 0.21, phastCons 1 |
| Overall | ||
| CADD | 9.453 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0669% | 1,496 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,926 |
| South Asian | 0.0011% | 91,056 |
| European (non-Finnish) | 8.48e-05% | 1,179,636 |
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.Pro205=
- Coding
- c.615C>G
- MANE Select
- NM_005214
- dbSNP
- rs74808460
- Type
- single nucleotide variant
- Location
- chr2:203872755 (GRCh38)
- Gene constraint
- LOEUF 0.211 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.67 · 22 PDB
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.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
- CTLA4 p.Pro136Leu Likely pathogenic ★★★ same condition
- CTLA4 p.Pro136Ser Likely pathogenic ★★★ same condition
- CTLA4 p.Pro137Arg 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-pro205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown