Is TRMT10A p.Arg91Cys (c.271C>T) pathogenic?

TRMT10A p.Arg91Cys (c.271C>T) is classified Uncertain significance in TRMT10A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-28). AlphaMissense: likely benign (0.2188); Ultra-rare (popmax 0.0134%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRMT10A p.Arg91Cys (c.271C>T)?

TRMT10A p.Arg91Cys (c.271C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRMT10A p.Arg91Cys (c.271C>T) in the general population?

TRMT10A p.Arg91Cys (c.271C>T) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about TRMT10A p.Arg91Cys (c.271C>T)?

AlphaMissense predicts likely benign (score 0.2188) — an in-silico prediction, not a clinical call.

TRMT10A p.Arg91Cys

c.271C>T · rs562796852 · VCV1951100

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2188 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2188	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.42 · regional, not allelic
Overall
CADD	26.3	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 0.0134% Admixed American · 8/59,776 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00484%

Overall 0.00105% 17/1,612,430 alleles · ultra-rare exomes 14/1,460,258 · genomes 3/152,172 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,472
East Asian	0.00671%	14,914
South Asian	0.0011%	90,776
European (non-Finnish)	0.000424%	235,854

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: TRMT10A
Protein: p.Arg91Cys
Coding: c.271C>T
MANE Select: NM_001134665
dbSNP: rs562796852
Type: single nucleotide variant
Location: chr4:99558126 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.77 · 1 PDB
Residue 91: the sam-dependent mtase trm10-type domain; a UniProt-annotated variant site (in mssgm1)

Full TRMT10A 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

TRMT10A p.Arg91= Likely benign ★ same residue
TRMT10A p.Glu27Ter Pathogenic ★★ same condition
TRMT10A p.Gly206Arg Pathogenic ★★ same condition
TRMT10A p.Arg58Gln Uncertain significance ★★ ⚠ same condition
TRMT10A p.Arg58Trp Uncertain significance ★★ ⚠ same condition
TRMT10A p.Arg61His Uncertain significance ★★ same condition
TRMT10A p.Arg69Cys Uncertain significance ★★ ⚠ same condition
TRMT10A p.Glu196Gly 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/trmt10a-p-arg91cys (accessed [today's date]).

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