Is TRMT5 p.Ser397Arg (c.1189A>C) pathogenic?

TRMT5 p.Ser397Arg (c.1189A>C) is classified Uncertain significance in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: likely benign (0.2247); Ultra-rare (popmax 0.0307%, afr); Associated with Inborn genetic diseases.

What condition is associated with TRMT5 p.Ser397Arg (c.1189A>C)?

TRMT5 p.Ser397Arg (c.1189A>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRMT5 p.Ser397Arg (c.1189A>C) in the general population?

TRMT5 p.Ser397Arg (c.1189A>C) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about TRMT5 p.Ser397Arg (c.1189A>C)?

AlphaMissense predicts likely benign (score 0.2247) — an in-silico prediction, not a clinical call.

TRMT5 p.Ser397Arg

c.1189A>C · VCV3461906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2247 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2247	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -4.6
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	14.45	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 0.0307% African / African-American · 23/74,922 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00173% 28/1,614,100 alleles · ultra-rare exomes 17/1,461,890 · genomes 11/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,257
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00167%	60,012

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.Ser397Arg
Coding: c.1189A>C
MANE Select: NM_020810
Type: single nucleotide variant
Location: chr14:60975730 (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

Disease context

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

Similar variants

TRMT5 p.Ser397Gly 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-ser397arg (accessed [today's date]).

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