CIT p.Leu1246=
c.3738C>G · VCV4779561
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0258%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.127 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -0.95, phastCons 1 |
| Overall | ||
| CADD | 7.141 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0258%
African / African-American · 19/73,608 alleles
Filtering AF
0.0169%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.014%
Overall
0.00126%
20/1,591,566 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0258% | 3,874 |
| East Asian | 0.00224% | 44,642 |
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
- CIT
- Protein
- p.Leu1246=
- Coding
- c.3738C>G
- MANE Select
- NM_001206999
- Type
- single nucleotide variant
- Location
- chr12:119720580 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.75
- Residue 1246
- the 'interaction with rho/rac' region
Similar variants
- CIT p.Arg1178Ter Pathogenic ★★ same type
- CIT p.Arg220Ter Pathogenic ★★ same type
- CIT c.4168+5G>A Uncertain significance ★★ same type
- CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same type
- CIT p.Ala1466Asp Uncertain significance ★★ ⚠ same type
- CIT p.Ala1527Val Uncertain significance ★★ ⚠ same type
- CIT p.Ala244Val Uncertain significance ★★ ⚠ same type
- CIT p.Ala495Ser 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/cit-p-leu1246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown