Is TRIM33 p.Ser71Phe (c.212C>T) pathogenic?

TRIM33 p.Ser71Phe (c.212C>T) is classified Uncertain significance in TRIM33 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: likely benign (0.1996); Very rare (popmax 0.00293%, eas).

How common is TRIM33 p.Ser71Phe (c.212C>T) in the general population?

TRIM33 p.Ser71Phe (c.212C>T) is very rare (popmax 0.00293%, eas) (gnomAD).

What do computational predictors say about TRIM33 p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely benign (score 0.1996) — an in-silico prediction, not a clinical call.

TRIM33 p.Ser71Phe

c.212C>T · rs777482424 · VCV2221032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00293%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1996	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP -0.041, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 366 bp · p 0.0016 · regional, not allelic
Overall
CADD	24.1	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 0.00293% East Asian · 1/34,124 alleles

Filtering AF 0.000528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000386%

Overall 0.000885% 13/1,468,776 alleles · very rare exomes 12/1,316,758 · genomes 1/152,018 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00293%	34,124
African / African-American	0.00147%	67,972
European (non-Finnish)	0.000985%	101,537

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.Ser71Phe
Coding: c.212C>T
MANE Select: NM_015906
dbSNP: rs777482424
Type: single nucleotide variant
Location: chr1:114510865 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.49 · 9 PDB
Residue 71: the 'necessary for e3 ubiquitin-protein ligase activity and repression of smad4 signaling and transcriptional repression' region; the 'disordered' region

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.Pro960= 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

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-ser71phe (accessed [today's date]).

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