Is RNMT p.Ile184Phe (c.550A>T) pathogenic?

RNMT p.Ile184Phe (c.550A>T) is classified Uncertain significance in RNMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely pathogenic (0.7367); Absent from gnomAD v4.1.

How common is RNMT p.Ile184Phe (c.550A>T) in the general population?

RNMT p.Ile184Phe (c.550A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNMT p.Ile184Phe (c.550A>T)?

AlphaMissense predicts likely pathogenic (score 0.7367) — an in-silico prediction, not a clinical call.

RNMT p.Ile184Phe

c.550A>T · VCV3947008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7367 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7367	likely pathogenic
REVEL	0.674	pathogenic-leaning
SaProt	LLR -13.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: RNMT
Protein: p.Ile184Phe
Coding: c.550A>T
MANE Select: NM_003799
Type: single nucleotide variant
Location: chr18:13734596 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 8 PDB
Residue 184: the mrna cap 0 methyltransferase domain; an α-helix

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

Similar variants

RNMT p.Tyr399= Benign ★★ same type
RNMT p.Ala151Val Uncertain significance ★ ⚠ same type
RNMT p.Ala2Thr Uncertain significance ★ ⚠ same type
RNMT p.Ala56Thr Uncertain significance ★ ⚠ same type
RNMT p.Arg107Gly Uncertain significance ★ ⚠ same type
RNMT p.Arg239Trp Uncertain significance ★ ⚠ same type
RNMT p.Arg247Cys Uncertain significance ★ ⚠ same type
RNMT p.Asn31Thr 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/rnmt-p-ile184phe (accessed [today's date]).

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