Is RNMT p.Cys73Tyr (c.218G>A) pathogenic?

RNMT p.Cys73Tyr (c.218G>A) is classified Uncertain significance in RNMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.058); Absent from gnomAD v4.1.

How common is RNMT p.Cys73Tyr (c.218G>A) in the general population?

RNMT p.Cys73Tyr (c.218G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNMT p.Cys73Tyr (c.218G>A)?

AlphaMissense predicts likely benign (score 0.058) — an in-silico prediction, not a clinical call.

RNMT p.Cys73Tyr

c.218G>A · VCV4155917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.058 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.058	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -6.87	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 0.92	GERP -4.7, phastCons 0.063
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	13.26	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: RNMT
Protein: p.Cys73Tyr
Coding: c.218G>A
MANE Select: NM_003799
Type: single nucleotide variant
Location: chr18:13731735 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 8 PDB
Residue 73: the 'disordered' region

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-cys73tyr (accessed [today's date]).

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