Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 9.34%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.121 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.8 | GERP -3.5 |
| Overall | ||
| CADD | 2.333 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.34%
African / African-American · 7,005/75,028 alleles
Filtering AF
9.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.08%
Overall
2.63%
42,464/1,613,964 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.34% | 11 |
| East Asian | 5.46% | 18 |
| Remaining individualsnot grpmax-eligible | 2.76% | 36 |
| Admixed American | 2.66% | 38 |
| Middle Eastern | 2.56% | 39 |
| European (non-Finnish) | 2.18% | 46 |
| South Asian | 2.18% | 46 |
| Ashkenazi Jewishnot grpmax-eligible | 2.14% | 47 |
| Finnishnot grpmax-eligible | 1.77% | 57 |
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
- COMT
- Protein
- p.Pro199=
- Coding
- c.597G>A
- MANE Select
- NM_000754
- dbSNP
- rs769224
- Type
- single nucleotide variant
- Location
- chr22:19964281 (GRCh38)
- Gene constraint
- LOEUF 1.128 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.07 · 12 PDB
- Residue 199
- an α-helix
Similar variants
- TXNRD2 p.Ala5Val Uncertain significance ★★ same type
- TXNRD2 p.Ala7Gly Uncertain significance ★★ same type
- TXNRD2 p.Ala7Val Uncertain significance ★★ same type
- TXNRD2 p.Arg9Pro Uncertain significance ★★ same type
- TXNRD2 p.Gly10Ala Uncertain significance ★★ same type
- TXNRD2 p.Gly10Val Uncertain significance ★★ same type
- TXNRD2 p.Leu8Val Uncertain significance ★★ same type
- TXNRD2 p.Met1Thr 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/comt-p-pro199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown