CIT p.Cys343=
c.1029C>T · rs145804827 · VCV791053
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.15%, nfe)
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 5.5 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 12.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.15%
European (non-Finnish) · 1,773/1,179,966 alleles
Filtering AF
0.144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.142%
Overall
0.118%
1,903/1,613,976 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.15% | 666 |
| Remaining individualsnot grpmax-eligible | 0.107% | 933 |
| Admixed American | 0.035% | 2,856 |
| Finnishnot grpmax-eligible | 0.025% | 4,000 |
| African / African-American | 0.02% | 5,001 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.00988% | 10,119 |
| East Asian | 0.00223% | 44,862 |
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.Cys343=
- Coding
- c.1029C>T
- MANE Select
- NM_001206999
- dbSNP
- rs145804827
- Type
- single nucleotide variant
- Location
- chr12:119822902 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.75
- Residue 343
- the protein kinase domain
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-cys343 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown