CIT p.Val1604=
c.4812C>T · rs146815718 · VCV2643384
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.074%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.277 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.18 | GERP -2.8, phastCons 0.86 |
| Overall | ||
| CADD | 9.479 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.074%
Admixed American · 44/59,476 alleles
Filtering AF
0.0566%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0505%
Overall
0.00639%
103/1,611,158 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.074% | 1,352 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,239 |
| South Asian | 0.00441% | 22,674 |
| European (non-Finnish) | 0.00365% | 27,407 |
| African / African-American | 0.00267% | 37,471 |
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.Val1604=
- Coding
- c.4812C>T
- MANE Select
- NM_001206999
- dbSNP
- rs146815718
- Type
- single nucleotide variant
- Location
- chr12:119712220 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.75
- Residue 1604
- the cnh 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-val1604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown