Is TRMT5 p.Asp486Val (c.1457A>T) pathogenic?

TRMT5 p.Asp486Val (c.1457A>T) is classified Uncertain significance in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.0757); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRMT5 p.Asp486Val (c.1457A>T)?

TRMT5 p.Asp486Val (c.1457A>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRMT5 p.Asp486Val (c.1457A>T) in the general population?

TRMT5 p.Asp486Val (c.1457A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRMT5 p.Asp486Val (c.1457A>T)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

TRMT5 p.Asp486Val

c.1457A>T · rs2036826633 · VCV2477091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.21 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.1	GERP -4.3, phastCons 0.079
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	18.63	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

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.Asp486Val
Coding: c.1457A>T
MANE Select: NM_020810
dbSNP: rs2036826633
Type: single nucleotide variant
Location: chr14:60975182 (GRCh38)
Gene constraint: LOEUF 0.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50
Residue 486: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRMT5 p.Asp486Tyr Uncertain significance ★ ⚠ same residue
TRMT5 p.Ala188Asp Uncertain significance ★★ ⚠ same condition
TRMT5 p.Ala45Thr Uncertain significance ★★ ⚠ same condition
TRMT5 p.Ala45Val Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg120Cys Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg125His Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg15Thr Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg266Gln Uncertain significance ★★ ⚠ same condition

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-asp486val (accessed [today's date]).

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