COMT p.Ala102=
c.306C>T · rs757949902 · VCV762891
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 -8.3 | GERP -3.3 |
| Overall | ||
| CADD | 0.304 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,066 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00717%
Overall
0.00409%
66/1,612,410 alleles · ultra-rare
exomes 65/1,460,226 · genomes 1/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,022 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| Finnishnot grpmax-eligible | 0.0048% | 20,825 |
| European (non-Finnish) | 0.00466% | 21,455 |
| African / African-American | 0.00133% | 74,910 |
| South Asian | 0.0011% | 91,080 |
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.Ala102=
- Coding
- c.306C>T
- MANE Select
- NM_000754
- dbSNP
- rs757949902
- Type
- single nucleotide variant
- Location
- chr22:19963582 (GRCh38)
- Gene constraint
- LOEUF 1.128 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.07 · 12 PDB
- Residue 102
- a UniProt-annotated variant site (in); an α-helix
Similar variants
- COMT p.Ala102Thr Benign/Likely benign ★★ same residue
- 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
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-ala102 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown