Is TRMT5 p.Cys321= (c.963C>T) pathogenic?

TRMT5 p.Cys321= (c.963C>T) is classified Likely benign in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). Absent from gnomAD v4.1.

How common is TRMT5 p.Cys321= (c.963C>T) in the general population?

TRMT5 p.Cys321= (c.963C>T) is absent from gnomAD v4.1 (gnomAD).

TRMT5 p.Cys321=

c.963C>T · rs2502985794 · VCV2777178

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.57	GERP -1.9, phastCons 0.99
Overall
CADD	6.192	PHRED · no single calibrated threshold — expert panels disagree

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: TRMT5
Protein: p.Cys321=
Coding: c.963C>T
MANE Select: NM_020810
dbSNP: rs2502985794
Type: single nucleotide variant
Location: chr14:60975956 (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.Cys321Arg Uncertain significance ★ ⚠ same residue
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

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-cys321 (accessed [today's date]).

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