Is TRIM58 p.Arg98Pro (c.293G>C) pathogenic?

TRIM58 p.Arg98Pro (c.293G>C) is classified Uncertain significance in TRIM58 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely benign (0.2069); Very rare (popmax 0.00419%, amr).

How common is TRIM58 p.Arg98Pro (c.293G>C) in the general population?

TRIM58 p.Arg98Pro (c.293G>C) is very rare (popmax 0.00419%, amr) (gnomAD).

What do computational predictors say about TRIM58 p.Arg98Pro (c.293G>C)?

AlphaMissense predicts likely benign (score 0.2069) — an in-silico prediction, not a clinical call.

TRIM58 p.Arg98Pro

c.293G>C · VCV3461484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00419%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2069	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.74	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 -1.5	GERP -3.7
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.17 · regional, not allelic
Overall
CADD	15.99	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00419% Admixed American · 1/23,882 alleles

Overall 7.8e-05% 1/1,282,100 alleles · very rare exomes 0/1,130,076 · genomes 1/152,024 · joint denominator

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: TRIM58
Protein: p.Arg98Pro
Coding: c.293G>C
MANE Select: NM_015431
Type: single nucleotide variant
Location: chr1:247857539 (GRCh38)
Gene constraint: LOEUF 1.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.32 · 2 PDB

Full TRIM58 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM58 p.Ala206Val Uncertain significance ★ ⚠ same type
TRIM58 p.Ala308Thr Uncertain significance ★ ⚠ same type
TRIM58 p.Ala356Thr Uncertain significance ★ ⚠ same type
TRIM58 p.Ala453Val Uncertain significance ★ ⚠ same type
TRIM58 p.Ala4Thr Uncertain significance ★ ⚠ same type
TRIM58 p.Ala93Thr Uncertain significance ★ ⚠ same type
TRIM58 p.Arg105Gly Uncertain significance ★ ⚠ same type
TRIM58 p.Arg181Cys 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/trim58-p-arg98pro (accessed [today's date]).

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