POP1 p.Ala166=
c.498C>T · rs748460495 · VCV1540212
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00602%, nfe)
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 -2.3 | GERP -3.8 |
| Overall | ||
| CADD | 0.999 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00602%
European (non-Finnish) · 71/1,179,902 alleles
Filtering AF
0.00486%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00447%
Overall
0.00471%
76/1,613,702 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00602% | 16,618 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| East Asian | 0.00446% | 22,446 |
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
- POP1
- Protein
- p.Ala166=
- Coding
- c.498C>T
- MANE Select
- NM_001199563 · reported on NM_001145860
- dbSNP
- rs748460495
- Type
- single nucleotide variant
- Location
- chr8:98129989 (GRCh38)
- Structure
- AlphaFold pLDDT 76.08
- Residue 166
- the 'required for interaction with kcnk2' region
Similar variants
- POP1 p.Ala166Pro Uncertain significance ★★ ⚠ same residue
- POP1 p.Gln778Ter Pathogenic/Likely pathogenic ★★ same type
- POP1 p.Val696Asp Likely pathogenic ★★ ⚠ same type
- POPDC1 p.Arg88Ter Pathogenic/Likely pathogenic ★★ same type
- POPDC1 p.Ser201Phe Likely pathogenic ★★ same type
- POP1 p.Ala1011Thr Uncertain significance ★★ ⚠ same type
- POP1 p.Ala44Pro Uncertain significance ★★ ⚠ same type
- POP1 p.Ala497Val 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/pop1-p-ala166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown