ASTN1 p.Arg1273Ser
c.3819G>C · VCV3388027
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.225%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.074 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.99, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 85 kb · p 0.052 · regional, not allelic |
| Overall | ||
| CADD | 22.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.225%
South Asian · 205/91,076 alleles
Filtering AF
0.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.19%
Overall
0.0609%
983/1,614,122 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.225% | 444 |
| Middle Eastern | 0.215% | 466 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0912% | 1,097 |
| Remaining individualsnot grpmax-eligible | 0.0768% | 1,302 |
| European (non-Finnish) | 0.0566% | 1,766 |
| Admixed American | 0.0233% | 4,288 |
| African / African-American | 0.00933% | 10,716 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
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.Arg1273Ser
- Coding
- c.3819G>C
- MANE Select
- NM_004319
- Type
- single nucleotide variant
- Location
- chr1:176864350 (GRCh38)
- Gene constraint
- LOEUF 0.392 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.88
- Residue 1273
- a disulfide bond
Similar variants
- 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
- ASTN1 p.Ala2Thr 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-arg1273ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown