Is TRMT1 p.Val72Ile (c.214G>A) pathogenic?

TRMT1 p.Val72Ile (c.214G>A) is classified Uncertain significance in TRMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.2359); Very rare (popmax 0.00297%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRMT1 p.Val72Ile (c.214G>A)?

TRMT1 p.Val72Ile (c.214G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRMT1 p.Val72Ile (c.214G>A) in the general population?

TRMT1 p.Val72Ile (c.214G>A) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about TRMT1 p.Val72Ile (c.214G>A)?

AlphaMissense predicts likely benign (score 0.2359) — an in-silico prediction, not a clinical call.

TRMT1 p.Val72Ile

c.214G>A · VCV4191365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2359	likely benign
REVEL	0.567	indeterminate
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.36	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.24 · regional, not allelic
Overall
CADD	32.0	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 0.00297% European (non-Finnish) · 35/1,180,032 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00223% 36/1,614,024 alleles · very rare exomes 35/1,461,856 · genomes 1/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,715
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: TRMT1
Protein: p.Val72Ile
Coding: c.214G>A
MANE Select: NM_001136035
Type: single nucleotide variant
Location: chr19:13116186 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68 · 1 PDB
Residue 72: the trm1 methyltransferase domain

Full TRMT1 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

TRMT1 p.Ala337Thr Uncertain significance ★★ ⚠ same condition
TRMT1 p.Ala343Val Uncertain significance ★★ ⚠ same condition
TRMT1 p.Arg358His Uncertain significance ★★ ⚠ same condition
TRMT1 p.Arg410Cys Uncertain significance ★★ ⚠ same condition
TRMT1 p.Asp449Asn Uncertain significance ★★ ⚠ same condition
TRMT1 p.Gly352Arg Uncertain significance ★★ ⚠ same condition
TRMT1 p.Gly42Glu Uncertain significance ★★ ⚠ same condition
TRMT1 p.Leu463Arg 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/trmt1-p-val72ile (accessed [today's date]).

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