Is RNMT p.Tyr399= (c.1197C>T) pathogenic?

RNMT p.Tyr399= (c.1197C>T) is classified Benign in RNMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-07). Rare (popmax 0.775%, nfe).

How common is RNMT p.Tyr399= (c.1197C>T) in the general population?

RNMT p.Tyr399= (c.1197C>T) is rare (popmax 0.775%, nfe) (gnomAD).

RNMT p.Tyr399=

c.1197C>T · rs115462439 · VCV773596

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.775%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.3, phastCons 1
Overall
CADD	10.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.775% European (non-Finnish) · 8,927/1,152,128 alleles

Filtering AF 0.761% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.756%

Overall 0.645% 10,154/1,574,236 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.08%	48
European (non-Finnish)grpmax	0.775%	129
Finnishnot grpmax-eligible	0.592%	169
Remaining individualsnot grpmax-eligible	0.532%	188
Ashkenazi Jewishnot grpmax-eligible	0.241%	415
Middle Eastern	0.201%	498
East Asian	0.194%	516
South Asian	0.189%	530
Admixed American	0.151%	663
African / African-American	0.119%	842

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr399=
Coding: c.1197C>T
MANE Select: NM_003799
dbSNP: rs115462439
Type: single nucleotide variant
Location: chr18:13746277 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 8 PDB
Residue 399: 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.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
RNMT p.Asn320Ser 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-tyr399 (accessed [today's date]).

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