Is COMT p.Ser267= (c.801C>T) pathogenic?

COMT p.Ser267= (c.801C>T) is classified Likely benign in COMT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-24). Very rare (popmax 0.00441%, sas); Associated with COMT-related disorder.

What condition is associated with COMT p.Ser267= (c.801C>T)?

COMT p.Ser267= (c.801C>T) is associated with COMT-related disorder (ClinVar).

How common is COMT p.Ser267= (c.801C>T) in the general population?

COMT p.Ser267= (c.801C>T) is very rare (popmax 0.00441%, sas) (gnomAD).

COMT p.Ser267=

c.801C>T · rs762482920 · VCV3054100

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00441%, sas)

Conditions

COMT-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.18	GERP -2.8
Overall
CADD	5.318	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00441% South Asian · 4/90,604 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000895%

Overall 0.000872% 14/1,604,694 alleles · very rare exomes 13/1,460,246 · genomes 1/144,448 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00441%	22,651
African / African-American	0.00273%	36,669
East Asian	0.00224%	44,636
Admixed American	0.0017%	58,792
Finnishnot grpmax-eligible	0.00162%	61,660
European (non-Finnish)	0.000425%	235,422

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.Ser267=
Coding: c.801C>T
MANE Select: NM_000754
dbSNP: rs762482920
Type: single nucleotide variant
Location: chr22:19968721 (GRCh38)

Full COMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COMT-related disorder

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-ser267 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown