Is COMT p.Asn39= (c.117C>T) pathogenic?

COMT p.Asn39= (c.117C>T) is classified Benign in COMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-10). Low-frequency (popmax 1.8%, sas).

How common is COMT p.Asn39= (c.117C>T) in the general population?

COMT p.Asn39= (c.117C>T) is low-frequency (popmax 1.8%, sas) (gnomAD).

COMT p.Asn39=

c.117C>T · rs74745580 · VCV717115

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.8%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.5	GERP -3.5
Overall
CADD	2.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.8% South Asian · 1,618/89,874 alleles

Filtering AF 1.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.7%

Overall 0.233% 3,735/1,604,504 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.72%	37
South Asiangrpmax	1.8%	56
Middle Eastern	0.728%	137
East Asian	0.436%	229
Remaining individualsnot grpmax-eligible	0.377%	265
Admixed American	0.188%	533
European (non-Finnish)	0.0608%	1,644
African / African-American	0.0254%	3,937
Finnishnot grpmax-eligible	0.00162%	61,742

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn39=
Coding: c.117C>T
MANE Select: NM_000754
dbSNP: rs74745580
Type: single nucleotide variant
Location: chr22:19962643 (GRCh38)
Gene constraint: LOEUF 1.128 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.07 · 12 PDB

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

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-asn39 (accessed [today's date]).

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