Is TRIM33 p.Pro960= (c.2880C>T) pathogenic?

TRIM33 p.Pro960= (c.2880C>T) is classified Benign in TRIM33 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-31). Common (popmax 8.82%, afr) — too common for a highly-penetrant pathogenic allele.

TRIM33 p.Pro960=

Q: How common is TRIM33 p.Pro960= (c.2880C>T) in the general population?

TRIM33 p.Pro960= (c.2880C>T) is common (popmax 8.82%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2880C>T · rs2179657 · VCV782385

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.82%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.084	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.2
Overall
CADD	7.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.82% African / African-American · 6,608/74,910 alleles

Filtering AF 8.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.57%

Overall 0.456% 7,348/1,612,914 alleles · common exomes 3,597/1,460,770 · genomes 3,751/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.82%	11
Remaining individualsnot grpmax-eligible	0.523%	191
Admixed American	0.456%	219
Middle Eastern	0.215%	466
South Asian	0.0286%	3,495
European (non-Finnish)	0.00865%	11,565

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: TRIM33
Protein: p.Pro960=
Coding: c.2880C>T
MANE Select: NM_015906
dbSNP: rs2179657
Type: single nucleotide variant
Location: chr1:114402772 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.49 · 9 PDB
Residue 960: the bromo domain; an α-helix

Full TRIM33 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM33 p.Gln382= Benign ★★ same type
TRIM33 p.Leu831= Benign ★★ same type
TRIM33 p.Pro629= Benign ★★ same type
TRIM33 p.Ala226Val Uncertain significance ★ ⚠ same type
TRIM33 p.Ala651Glu Uncertain significance ★ ⚠ same type
TRIM33 p.Ala761Thr Uncertain significance ★ ⚠ same type
TRIM33 p.Ala832Val Uncertain significance ★ ⚠ same type
TRIM33 p.Arg1116His 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/trim33-p-pro960 (accessed [today's date]).

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