A2M p.Thr548=
c.1644C>T · rs745823596 · VCV3057371
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.72 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.48 | GERP -3.4 |
| Overall | ||
| CADD | 2.645 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,766 alleles
Filtering AF
0.00625%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00244%
39/1,597,934 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,307 |
| South Asian | 0.0057% | 17,556 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,312 |
| East Asian | 0.00225% | 44,390 |
| European (non-Finnish) | 0.00188% | 53,271 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,012 |
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
- A2M
- Protein
- p.Thr548=
- Coding
- c.1644C>T
- MANE Select
- NM_000014
- dbSNP
- rs745823596
- Type
- single nucleotide variant
- Location
- chr12:9099438 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.61 · 13 PDB
- Residue 548
- a disulfide bond
Similar variants
- A2M c.3756+4G>A Benign/Likely benign ★★ same type
- A2M p.Ala844= Benign ★★ same type
- A2M p.Asp277Asn Benign ★★ same type
- A2M p.Ile1000Val Benign ★★ same type
- A2M p.Pro261Leu Benign ★★ ⚠ same type
- A2M p.Tyr1152= Benign/Likely benign ★★ same type
- A2M p.Val120= Likely benign ★★ same type
- A2M p.Val129= Benign ★★ 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/a2m-p-thr548 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown