CIT p.Pro1377=
c.4131G>A · rs755717565 · VCV3031222
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
CIT-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.046 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.6 | GERP -3.6 |
| Overall | ||
| CADD | 8.776 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,868 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.000806%
13/1,613,554 alleles · very rare
exomes 13/1,461,248 · genomes 0/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,434 |
| Admixed American | 0.00167% | 59,970 |
| European (non-Finnish) | 0.000848% | 117,967 |
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.Pro1377=
- Coding
- c.4131G>A
- MANE Select
- NM_001206999
- dbSNP
- rs755717565
- Type
- single nucleotide variant
- Location
- chr12:119718282 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.75
Disease context
CIT-related disorder
Similar variants
- CIT p.Pro1377Leu Uncertain significance ★★ ⚠ same residue
- CIT p.Gln64Ter Likely pathogenic ★ same condition
- CIT c.2532-9C>T Likely benign same condition
- CIT c.3486+7G>A Likely benign same condition
- CIT c.6187-4C>T Likely benign same condition
- CIT p.Asn1972= Likely benign same condition
- CIT p.Ile1356= Likely benign same condition
- CIT p.Leu1803= Likely benign 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/cit-p-pro1377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown