Is TRMT5 p.Pro487Ser (c.1459C>T) pathogenic?

TRMT5 p.Pro487Ser (c.1459C>T) is classified Conflicting classifications of pathogenicity in TRMT5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.0843); Ultra-rare (popmax 0.0525%, mid); Associated with Inborn genetic diseases.

What condition is associated with TRMT5 p.Pro487Ser (c.1459C>T)?

TRMT5 p.Pro487Ser (c.1459C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRMT5 p.Pro487Ser (c.1459C>T) in the general population?

TRMT5 p.Pro487Ser (c.1459C>T) is ultra-rare (popmax 0.0525%, mid) (gnomAD).

What do computational predictors say about TRMT5 p.Pro487Ser (c.1459C>T)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

TRMT5 p.Pro487Ser

c.1459C>T · rs147405788 · VCV1645348

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0525%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0525% Middle Eastern · 3/5,712 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0414%

Overall 0.0441% 708/1,605,578 alleles · ultra-rare exomes 651/1,453,394 · genomes 57/152,184 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.205%	487
Middle Easterngrpmax	0.0525%	1,904
European (non-Finnish)	0.0459%	2,180
Remaining individualsnot grpmax-eligible	0.0241%	4,142
South Asian	0.00893%	11,198
Admixed American	0.00867%	11,532
African / African-American	0.00807%	12,397

Finnish 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: TRMT5
Protein: p.Pro487Ser
Coding: c.1459C>T
MANE Select: NM_020810
dbSNP: rs147405788
Type: single nucleotide variant
Location: chr14:60975180 (GRCh38)
Gene constraint: LOEUF 0.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50
Residue 487: 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.Pro487= Benign ★★ 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-pro487ser (accessed [today's date]).

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