Is COMTD1 p.Pro162His (c.485C>A) pathogenic?

COMTD1 p.Pro162His (c.485C>A) is classified Uncertain significance in COMTD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.3154); Absent from gnomAD v4.1.

How common is COMTD1 p.Pro162His (c.485C>A) in the general population?

COMTD1 p.Pro162His (c.485C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMTD1 p.Pro162His (c.485C>A)?

AlphaMissense predicts likely benign (score 0.3154) — an in-silico prediction, not a clinical call.

COMTD1 p.Pro162His

c.485C>A · VCV3495932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3154 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,526,976)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3154	likely benign
REVEL	0.584	indeterminate
SaProt	LLR -13.56	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,852 bp · p 0.73 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,526,976). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COMTD1
Protein: p.Pro162His
Coding: c.485C>A
MANE Select: NM_144589
Type: single nucleotide variant
Location: chr10:75234955 (GRCh38)
Gene constraint: LOEUF 1.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.67 · 1 PDB

Full COMTD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMTD1 p.Ala126Thr Uncertain significance ★ ⚠ same type
COMTD1 p.Ala126Val Uncertain significance ★ ⚠ same type
COMTD1 p.Ala186Thr Uncertain significance ★ ⚠ same type
COMTD1 p.Ala91Gly Uncertain significance ★ ⚠ same type
COMTD1 p.Arg129Leu Uncertain significance ★ ⚠ same type
COMTD1 p.Arg129Pro Uncertain significance ★ ⚠ same type
COMTD1 p.Arg144Trp Uncertain significance ★ ⚠ same type
COMTD1 p.Arg212Lys 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/comtd1-p-pro162his (accessed [today's date]).

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