Is TRMT5 p.Val164fs (c.489dup) pathogenic?

TRMT5 p.Val164fs (c.489dup) is classified Uncertain significance in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-24). Very rare (popmax 0.0011%, nfe).

How common is TRMT5 p.Val164fs (c.489dup) in the general population?

TRMT5 p.Val164fs (c.489dup) is very rare (popmax 0.0011%, nfe) (gnomAD).

TRMT5 p.Val164fs

c.489dup · rs1172825880 · VCV1376851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,014 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,614,100 alleles · very rare exomes 13/1,461,854 · genomes 0/152,246 · 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.Val164fs
Coding: c.489dup
MANE Select: NM_020810
dbSNP: rs1172825880
Type: Duplication
Location: chr14:60979408 (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 c.12-21dup Benign/Likely benign ★★ same type
TRMT5 p.Lys181Ter Uncertain significance ★ same type
TRMT5 c.792+8_792+12dup Likely benign ★ same type
TRMT5 c.793-4dup Benign ★ 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-val164fs (accessed [today's date]).

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