POT1 p.Ala490=
c.1470A>G · rs1194907316 · VCV1773340
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, sas)
Conditions
2
tumor predisposition syndrome 3
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 0.05 | GERP -0.84, phastCons 0.085 |
| Overall | ||
| CADD | 6.481 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,074 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.00062%
10/1,613,974 alleles · ultra-rare
exomes 10/1,461,794 · genomes 0/152,180 · joint denominator
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
- POT1
- Protein
- p.Ala490=
- Coding
- c.1470A>G
- MANE Select
- NM_015450
- dbSNP
- rs1194907316
- Type
- single nucleotide variant
- Location
- chr7:124835314 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.63 · 14 PDB
Similar variants
- POT1 p.Ala490Thr Uncertain significance ★★ ⚠ same residue
- POT1 c.10-2A>C Pathogenic/Likely pathogenic ★★ same condition
- POT1 c.1163+1G>A Likely pathogenic ★★ same condition
- POT1 c.1164-1G>A Pathogenic/Likely pathogenic ★★ same condition
- POT1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same condition
- POT1 c.124+2T>C Likely pathogenic ★★ same condition
- POT1 c.125-2A>G Likely pathogenic ★★ same condition
- POT1 c.1369+1G>A Likely pathogenic ★★ 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/pot1-p-ala490 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown