ADD1 p.Pro398=
c.1194T>A · rs138254700 · VCV790310
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.478%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.045 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.059 | GERP -3.8, phastCons 0.83 |
| Overall | ||
| CADD | 6.867 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.478%
Middle Eastern · 29/6,062 alleles
Filtering AF
0.342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.296%
Overall
0.074%
1,195/1,614,220 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.478% | 209 |
| Admixed American | 0.327% | 306 |
| Remaining individualsnot grpmax-eligible | 0.219% | 456 |
| South Asian | 0.0955% | 1,047 |
| African / African-American | 0.0919% | 1,088 |
| European (non-Finnish) | 0.0554% | 1,804 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0338% | 2,960 |
| East Asian | 0.0201% | 4,987 |
| Finnishnot grpmax-eligible | 0.00625% | 16,011 |
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
- ADD1
- Protein
- p.Pro398=
- Coding
- c.1194T>A
- MANE Select
- NM_001354761
- dbSNP
- rs138254700
- Type
- single nucleotide variant
- Location
- chr4:2904796 (GRCh38)
- Gene constraint
- LOEUF 0.387 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 65.73
Similar variants
- ADD1 p.Val234= Benign ★★ same type
- ADD1 p.Val559Met Benign ★★ same type
- ADD1 c.2047+530G>A Uncertain significance ★ same type
- ADD1 c.2047+541G>T Uncertain significance ★ same type
- ADD1 p.Ala137Val Uncertain significance ★ ⚠ same type
- ADD1 p.Ala151Thr Uncertain significance ★ ⚠ same type
- ADD1 p.Ala156Thr Uncertain significance ★ ⚠ same type
- ADD1 p.Ala18Thr 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/add1-p-pro398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown