Is TRMT5 p.Ala445= (c.1335A>G) pathogenic?

TRMT5 p.Ala445= (c.1335A>G) is classified Likely benign in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). Ultra-rare (popmax 0.0147%, afr).

How common is TRMT5 p.Ala445= (c.1335A>G) in the general population?

TRMT5 p.Ala445= (c.1335A>G) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

TRMT5 p.Ala445=

c.1335A>G · rs564334343 · VCV2172025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.1	GERP -4.6
Overall
CADD	1.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/75,054 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00632%

Overall 0.000743% 12/1,614,218 alleles · ultra-rare exomes 6/1,461,880 · genomes 6/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,823
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Ala445=
Coding: c.1335A>G
MANE Select: NM_020810
dbSNP: rs564334343
Type: single nucleotide variant
Location: chr14:60975584 (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

Similar variants

TRMT5 p.Ala445Thr Uncertain significance ★ ⚠ same residue
TRMT5 p.Ala445Val Uncertain significance ★ ⚠ same residue
TRMT5 p.Ala188Asp Uncertain significance ★★ ⚠ same type
TRMT5 p.Ala45Thr Uncertain significance ★★ ⚠ same type
TRMT5 p.Ala45Val Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg120Cys Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg125His Uncertain significance ★★ ⚠ same type
TRMT5 p.Arg15Thr Uncertain significance ★★ ⚠ same type

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-ala445 (accessed [today's date]).

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