Is INMT p.Pro33His (c.98C>A) pathogenic?

INMT p.Pro33His (c.98C>A) is classified Uncertain significance in INMT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.1803); Absent from gnomAD v4.1.

How common is INMT p.Pro33His (c.98C>A) in the general population?

INMT p.Pro33His (c.98C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INMT p.Pro33His (c.98C>A)?

AlphaMissense predicts likely benign (score 0.1803) — an in-silico prediction, not a clinical call.

INMT p.Pro33His

c.98C>A · rs754241642 · VCV2337804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1803 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1803	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.6, phastCons 0.008
Regional constraint	o/e 0.94	unconstrained · MANE · 3,697 bp · p 0.27 · regional, not allelic
Overall
CADD	15.57	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INMT
Protein: p.Pro33His
Coding: c.98C>A
MANE Select: NM_006774
dbSNP: rs754241642
Type: single nucleotide variant
Location: chr7:30752248 (GRCh38)
Gene constraint: LOEUF 1.467 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.14 · 1 PDB
Residue 33: an α-helix

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

Similar variants

INMT c.363-7T>A Likely benign ★★ same type
INMT p.Ala104Thr Uncertain significance ★ ⚠ same type
INMT p.Ala134Glu Uncertain significance ★ ⚠ same type
INMT p.Ala215Thr Uncertain significance ★ ⚠ same type
INMT p.Ala247Ser Uncertain significance ★ ⚠ same type
INMT p.Ala247Val Uncertain significance ★ ⚠ same type
INMT p.Arg137Trp Uncertain significance ★ ⚠ same type
INMT p.Arg177His 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/inmt-p-pro33his (accessed [today's date]).

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