CIT p.Asp541=
c.1623T>C · rs139550316 · VCV728023
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.74%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.203 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.57 | GERP -3.5, phastCons 0.94 |
| Overall | ||
| CADD | 8.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.74%
East Asian · 780/44,888 alleles
Filtering AF
1.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.6%
Overall
0.0509%
822/1,614,154 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.74% | 58 |
| Remaining individualsnot grpmax-eligible | 0.0416% | 2,404 |
| South Asian | 0.00769% | 13,012 |
| Admixed American | 0.00667% | 15,004 |
| European (non-Finnish) | 0.000424% | 236,007 |
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.Asp541=
- Coding
- c.1623T>C
- MANE Select
- NM_001206999
- dbSNP
- rs139550316
- Type
- single nucleotide variant
- Location
- chr12:119782560 (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-p-asp541 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown