CEMIP p.Pro556=
c.1668G>A · rs377174220 · VCV3046778
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.049%, eas)
Conditions
1
CEMIP-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -5.5 |
| Overall | ||
| CADD | 3.282 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.049%
East Asian · 22/44,872 alleles
Filtering AF
0.0332%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0279%
Overall
0.007%
113/1,614,112 alleles · ultra-rare
exomes 103/1,461,892 · genomes 10/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.049% | 2,040 |
| South Asian | 0.0209% | 4,793 |
| Middle Eastern | 0.0165% | 6,060 |
| Admixed American | 0.0133% | 7,502 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| European (non-Finnish) | 0.00466% | 21,455 |
| African / African-American | 0.004% | 25,008 |
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
- CEMIP
- Protein
- p.Pro556=
- Coding
- c.1668G>A
- MANE Select
- NM_001293298
- dbSNP
- rs377174220
- Type
- single nucleotide variant
- Location
- chr15:80909177 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.69
- Residue 556
- the 'necessary for its endoplasmic reticulum (er) retention and interaction with hspa5' region
Disease context
CEMIP-related disorder
Similar variants
- CEMIP p.Pro556Leu Uncertain significance ★ ⚠ same residue
- CEMIP c.241+8A>G Likely benign same condition
- CEMIP p.Ala463Thr Likely benign same condition
- CEMIP p.Asp929= Benign same condition
- CEMIP p.Ile194= Likely benign same condition
- CEMIP p.Ile478= Likely benign same condition
- CEMIP p.Leu107= Likely benign same condition
- CEMIP p.Leu1138= 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/cemip-p-pro556 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown