A2ML1 p.Thr53=
c.159G>T · rs767370461 · VCV2449325
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0264%, sas)
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 -0.79 | GERP -3.3 |
| Overall | ||
| CADD | 0.443 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0264%
South Asian · 24/91,076 alleles
Filtering AF
0.0181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0154%
Overall
0.00155%
25/1,614,020 alleles · ultra-rare
exomes 19/1,461,866 · genomes 6/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0264% | 3,795 |
| European (non-Finnish) | 8.47e-05% | 1,179,984 |
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
- A2ML1
- Protein
- p.Thr53=
- Coding
- c.159G>T
- MANE Select
- NM_144670
- dbSNP
- rs767370461
- Type
- single nucleotide variant
- Location
- chr12:8823278 (GRCh38)
- Gene constraint
- LOEUF 0.953 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.61 · 5 PDB
- Residue 53
- a β-strand
Similar variants
- A2ML1 p.Thr53Arg Benign/Likely benign ★★ ⚠ same residue
- A2ML1 p.Thr53Met Uncertain significance ★ ⚠ same residue
- A2ML1 c.1834-1G>T Uncertain significance ★★ same type
- A2ML1 c.3264+4C>T Uncertain significance ★★ same type
- A2ML1 c.3933+4A>G Uncertain significance ★★ same type
- A2ML1 c.409+1G>A Uncertain significance ★★ same type
- A2ML1 c.4221+2T>C Uncertain significance ★★ same type
- A2ML1 c.*1+1G>A 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/a2ml1-p-thr53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown