A2ML1 p.Ser35=
c.105C>T · rs201185025 · VCV695806
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0545%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor loss, 42 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.24 | loss · gain 0.10 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -3.3 |
| Overall | ||
| CADD | 8.676 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0545%
European (non-Finnish) · 643/1,179,992 alleles
Filtering AF
0.051%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0496%
Overall
0.0432%
697/1,613,848 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0545% | 1,835 |
| Middle Eastern | 0.0329% | 3,042 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,288 |
| Finnishnot grpmax-eligible | 0.0187% | 5,335 |
| African / African-American | 0.012% | 8,322 |
| Admixed American | 0.01% | 9,994 |
| South Asian | 0.00549% | 18,206 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,592 |
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.Ser35=
- Coding
- c.105C>T
- MANE Select
- NM_144670
- dbSNP
- rs201185025
- Type
- single nucleotide variant
- Location
- chr12:8823224 (GRCh38)
- Gene constraint
- LOEUF 0.953 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.61 · 5 PDB
- Residue 35
- a β-strand
Similar variants
- 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
- A2ML1 p.Ala1002Val Uncertain significance ★★ ⚠ same type
- A2ML1 p.Ala1039Val 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-ser35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown