ASTN1 p.Pro600Ser
c.1798C>T · rs201822123 · VCV2521454
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00992%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.398 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.85 | unconstrained · MANE · 215 kb · p 7.5e-06 · regional, not allelic |
| Overall | ||
| CADD | 26.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00992%
European (non-Finnish) · 117/1,179,984 alleles
Filtering AF
0.00842%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00787%
Overall
0.00756%
122/1,613,906 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00992% | 10,085 |
| Admixed American | 0.00333% | 29,990 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| African / African-American | 0.00133% | 74,910 |
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
- ASTN1
- Protein
- p.Pro600Ser
- Coding
- c.1798C>T
- MANE Select
- NM_004319
- dbSNP
- rs201822123
- Type
- single nucleotide variant
- Location
- chr1:176957767 (GRCh38)
- Gene constraint
- LOEUF 0.392 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.88
Similar variants
- ASTN1 p.Pro600Leu Uncertain significance ★ same residue
- ASTN1 p.Asp1150Tyr Uncertain significance ★★ same type
- ASTN1 p.His419Asn Uncertain significance ★★ same type
- ASTN1 p.Ser290Gly Uncertain significance ★★ same type
- ASTN1 p.Val1025Leu Uncertain significance ★★ same type
- ASTN1 p.Arg1112Ter Likely pathogenic ★ same type
- ASTN1 p.Gly742Arg Likely pathogenic ★ same type
- ASTN1 c.1523+1G>T 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/astn1-p-pro600ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown