POR p.Val593Met
c.1777G>A · rs1398576378 · VCV3216808
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00544%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.778 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | phastCons 1 |
| Overall | ||
| CADD | 29.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00544%
African / African-American · 4/73,584 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00106%
Overall
0.000705%
11/1,560,614 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00544% | 18,396 |
| Admixed American | 0.00386% | 25,878 |
| South Asian | 0.00235% | 42,466 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,644 |
| European (non-Finnish) | 0.000173% | 576,675 |
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
- POR
- Protein
- p.Val593Met
- Coding
- c.1777G>A
- MANE Select
- NM_001395413
- dbSNP
- rs1398576378
- Type
- single nucleotide variant
- Location
- chr7:75986039 (GRCh38)
- Gene constraint
- LOEUF 0.887 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.29 · 14 PDB
- Residue 593
- a β-strand
Similar variants
- POR p.Ala102Thr Uncertain significance ★★ same condition
- POR p.Ala255Val Uncertain significance ★★ same condition
- POR p.Ala329Thr Uncertain significance ★★ same condition
- POR p.Arg191Gln Uncertain significance ★★ same condition
- POR p.Arg191Trp Uncertain significance ★★ same condition
- POR p.Arg265Trp Uncertain significance ★★ same condition
- POR p.Asp129Asn Uncertain significance ★★ same condition
- POR p.Gln272Arg Uncertain significance ★★ 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/por-p-val593met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown