ANTXR1 p.Pro421=
c.1263G>A · rs370893520 · VCV2164627
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.025%, amr)
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 -9.3 | GERP -3.4 |
| Overall | ||
| CADD | 0.291 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.025%
Admixed American · 15/59,994 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.00409%
66/1,614,008 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.025% | 4,000 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| East Asian | 0.00445% | 22,451 |
| European (non-Finnish) | 0.00364% | 27,443 |
| South Asian | 0.0022% | 45,542 |
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
- ANTXR1
- Protein
- p.Pro421=
- Coding
- c.1263G>A
- MANE Select
- NM_032208
- dbSNP
- rs370893520
- Type
- single nucleotide variant
- Location
- chr2:69182570 (GRCh38)
- Gene constraint
- LOEUF 0.346 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 72.76 · 5 PDB
- Residue 421
- the 'disordered' region
Similar variants
- ATR p.Ser421Gly Uncertain significance ★★ ⚠ same residue
- ATR p.Ser421Asn Uncertain significance ★ ⚠ same residue
- ANTXR1 p.Arg169Ter Pathogenic/Likely pathogenic ★★ same type
- ATR c.2533-1G>A Likely pathogenic ★★ same type
- ATR c.2634-1G>A Likely pathogenic ★★ same type
- ATR c.5196+1G>A Pathogenic/Likely pathogenic ★★ same type
- ATR c.6897+464C>G Pathogenic/Likely pathogenic ★★ same type
- ATR c.7042-1G>A Likely pathogenic ★★ 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/antxr1-p-pro421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown