PROM1 p.Glu751=
c.2253A>G · rs368580524 · VCV1122309
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.215%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.06 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -1.5, phastCons 0.095 |
| Overall | ||
| CADD | 2.203 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.215%
Middle Eastern · 8/3,728 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0779%
Overall
0.016%
226/1,414,416 alleles · rare
exomes 185/1,318,586 · genomes 41/95,830 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.215% | 466 |
| Admixed American | 0.102% | 979 |
| Remaining individualsnot grpmax-eligible | 0.0353% | 2,835 |
| European (non-Finnish) | 0.0139% | 7,219 |
| African / African-American | 0.00645% | 15,492 |
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
- PROM1
- Protein
- p.Glu751=
- Coding
- c.2253A>G
- MANE Select
- NM_006017
- dbSNP
- rs368580524
- Type
- single nucleotide variant
- Location
- chr4:15985787 (GRCh38)
- Gene constraint
- LOEUF 1.104 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.68
Similar variants
- PROM1 c.1142-1G>A Pathogenic/Likely pathogenic ★★ same type
- PROM1 c.1301+1G>A Pathogenic/Likely pathogenic ★★ same type
- PROM1 c.1301+2T>C Pathogenic/Likely pathogenic ★★ same type
- PROM1 c.1578+1G>A Pathogenic/Likely pathogenic ★★ same type
- PROM1 c.1579-1G>C Pathogenic ★★ same type
- PROM1 c.1579-2A>C Pathogenic/Likely pathogenic ★★ same type
- PROM1 c.1984-1G>T Pathogenic ★★ same type
- PROM1 c.2131-1G>A Pathogenic/Likely pathogenic ★★ 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/prom1-p-glu751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown