Is TRIM24 p.Pro682Arg (c.2045C>G) pathogenic?

TRIM24 p.Pro682Arg (c.2045C>G) is classified Uncertain significance in TRIM24 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.8159); Very rare (popmax 0.00017%, nfe).

How common is TRIM24 p.Pro682Arg (c.2045C>G) in the general population?

TRIM24 p.Pro682Arg (c.2045C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about TRIM24 p.Pro682Arg (c.2045C>G)?

AlphaMissense predicts likely pathogenic (score 0.8159) — an in-silico prediction, not a clinical call.

TRIM24 p.Pro682Arg

c.2045C>G · VCV4190454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8159 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8159	likely pathogenic
REVEL	0.531	indeterminate
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 54 kb · p 4.1e-10 · regional, not allelic
Overall
CADD	27.5	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 0.00017% European (non-Finnish) · 2/1,179,808 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,842 alleles · very rare exomes 2/1,461,612 · genomes 0/152,230 · 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: TRIM24
Protein: p.Pro682Arg
Coding: c.2045C>G
MANE Select: NM_015905
Type: single nucleotide variant
Location: chr7:138576403 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.84 · 22 PDB
Residue 682: the 'disordered' region

Full TRIM24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM24 p.Asp872Glu Benign ★★ ⚠ same type
TRIM24 p.Arg684Cys Likely pathogenic ★ same type
TRIM24 p.Ala262Val Uncertain significance ★ ⚠ same type
TRIM24 p.Ala550Thr Uncertain significance ★ ⚠ same type
TRIM24 p.Ala603Pro Uncertain significance ★ ⚠ same type
TRIM24 p.Ala603Ser Uncertain significance ★ ⚠ same type
TRIM24 p.Arg1036Gln Uncertain significance ★ ⚠ same type
TRIM24 p.Arg1046Cys 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/trim24-p-pro682arg (accessed [today's date]).

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