CIT c.1665+40T>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 58.1%, amr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +40 | near-intronic (+40 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.5 | GERP -3 |
| Non-coding constraint | Z 1.46 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 0.111 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
58.1%
Admixed American · 34,260/58,928 alleles
Filtering AF
57.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 57.4%
Overall
46.8%
749,875/1,602,542 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 58.1% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 54.9% | 2 |
| Middle Eastern | 52.2% | 2 |
| Finnishnot grpmax-eligible | 50% | 2 |
| Remaining individualsnot grpmax-eligible | 47.4% | 2 |
| European (non-Finnish) | 46.9% | 2 |
| South Asian | 46% | 2 |
| East Asian | 39.9% | 3 |
| Amishnot grpmax-eligible | 37.9% | 3 |
| African / African-American | 34.6% | 3 |
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
- Coding
- c.1665+40T>C
- MANE Select
- NM_001206999
- dbSNP
- rs440299
- Type
- single nucleotide variant
- Location
- chr12:119782478 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.75
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-c-1665-plus-40t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown