Is RNMT p.Asp133Asn (c.397G>A) pathogenic?

RNMT p.Asp133Asn (c.397G>A) is classified Uncertain significance in RNMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely benign (0.0666); Ultra-rare (popmax 0.015%, afr).

How common is RNMT p.Asp133Asn (c.397G>A) in the general population?

RNMT p.Asp133Asn (c.397G>A) is ultra-rare (popmax 0.015%, afr) (gnomAD).

What do computational predictors say about RNMT p.Asp133Asn (c.397G>A)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

RNMT p.Asp133Asn

c.397G>A · VCV3434627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	22.5	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

Grpmax group 0.015% African / African-American · 11/73,228 alleles

Filtering AF 0.00834% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00647%

Overall 0.000816% 13/1,593,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.015%	6,657
South Asian	0.0023%	43,481

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: RNMT
Protein: p.Asp133Asn
Coding: c.397G>A
MANE Select: NM_003799
Type: single nucleotide variant
Location: chr18:13731914 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 8 PDB
Residue 133: 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-asp133asn (accessed [today's date]).

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