CIT p.Phe375=
c.1125C>T · rs200757503 · VCV2173063
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0351%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.558 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.26 | acceptor loss · deltas |
| Pangolin | Δ0.29 | gain · loss 0.24 · SpliceAI calls loss · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 15.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0351%
East Asian · 15/42,710 alleles
Filtering AF
0.0216%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0174%
Overall
0.0021%
33/1,570,490 alleles · ultra-rare
exomes 29/1,418,202 · genomes 4/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0351% | 2,847 |
| Remaining individualsnot grpmax-eligible | 0.00331% | 30,205 |
| European (non-Finnish) | 0.00138% | 72,671 |
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.Phe375=
- Coding
- c.1125C>T
- MANE Select
- NM_001206999
- dbSNP
- rs200757503
- Type
- single nucleotide variant
- Location
- chr12:119803376 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.75
- Residue 375
- the agc-kinase c-terminal domain
Similar variants
- CIT p.Phe375fs Likely pathogenic ★ same residue
- 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
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-phe375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown