Is TRIM58 p.Pro302Arg (c.905C>G) pathogenic?

TRIM58 p.Pro302Arg (c.905C>G) is classified Uncertain significance in TRIM58 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: ambiguous (0.4141); Very rare (popmax 0.000509%, nfe).

How common is TRIM58 p.Pro302Arg (c.905C>G) in the general population?

TRIM58 p.Pro302Arg (c.905C>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about TRIM58 p.Pro302Arg (c.905C>G)?

AlphaMissense predicts ambiguous (score 0.4141) — an in-silico prediction, not a clinical call.

TRIM58 p.Pro302Arg

c.905C>G · VCV3973630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4141	ambiguous
REVEL	0.212	benign-leaning
SaProt	LLR -11.22	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.17 · regional, not allelic
Overall
CADD	22.4	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 0.000509% European (non-Finnish) · 6/1,179,836 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,784 alleles · very rare exomes 6/1,461,488 · genomes 0/152,296 · 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.Pro302Arg
Coding: c.905C>G
MANE Select: NM_015431
Type: single nucleotide variant
Location: chr1:247875933 (GRCh38)
Gene constraint: LOEUF 1.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.32 · 2 PDB
Residue 302: the b30.2/spry domain

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-pro302arg (accessed [today's date]).

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