ADD2 p.Pro231=
c.693G>A · VCV4236783
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0222%, 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 -20 | GERP -5.2 |
| Overall | ||
| CADD | 1.383 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0222%
Admixed American · 12/53,984 alleles
Filtering AF
0.0128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.01%
Overall
0.00343%
54/1,572,832 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0222% | 4,499 |
| South Asian | 0.00352% | 28,381 |
| European (non-Finnish) | 0.00328% | 30,484 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,568 |
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
- ADD2
- Protein
- p.Pro231=
- Coding
- c.693G>A
- MANE Select
- NM_001617
- Type
- single nucleotide variant
- Location
- chr2:70692415 (GRCh38)
- Gene constraint
- LOEUF 0.388 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.51
Similar variants
- ADD2 p.Asp28Asn Benign ★★ ⚠ same type
- ADD2 p.Glu335Asp Benign ★★ same type
- ADD2 p.Gly17Glu Benign ★★ same type
- ADD2 p.Ala150Val Uncertain significance ★ ⚠ same type
- ADD2 p.Ala232Gly Uncertain significance ★ ⚠ same type
- ADD2 p.Ala312Thr Uncertain significance ★ ⚠ same type
- ADD2 p.Ala418Pro Uncertain significance ★ ⚠ same type
- ADD2 p.Ala606Val 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/add2-p-pro231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown