Is TRMT5 p.Pro330= (c.990T>C) pathogenic?

TRMT5 p.Pro330= (c.990T>C) is classified Likely benign in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). Very rare (popmax 0.000124%).

How common is TRMT5 p.Pro330= (c.990T>C) in the general population?

TRMT5 p.Pro330= (c.990T>C) is very rare (popmax 0.000124%) (gnomAD).

TRMT5 p.Pro330=

c.990T>C · rs2502985730 · VCV1946509

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	6.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000124%

Overall 0.000124% 2/1,614,200 alleles · very rare exomes 2/1,461,888 · genomes 0/152,312 · joint denominator

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: TRMT5
Protein: p.Pro330=
Coding: c.990T>C
MANE Select: NM_020810
dbSNP: rs2502985730
Type: single nucleotide variant
Location: chr14:60975929 (GRCh38)
Gene constraint: LOEUF 0.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50

Full TRMT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRMT5 p.Ala188Asp Uncertain significance ★★ ⚠ same type
TRMT5 p.Ala45Thr Uncertain significance ★★ ⚠ same type
TRMT5 p.Ala45Val Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg120Cys Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg125His Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg15Thr Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg266Gln Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg291His 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/trmt5-p-pro330 (accessed [today's date]).

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