Is TRIM28 p.Ala397= (c.1191C>T) pathogenic?

TRIM28 p.Ala397= (c.1191C>T) is classified Likely benign in TRIM28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Very rare (popmax 0.00263%, nfe).

How common is TRIM28 p.Ala397= (c.1191C>T) in the general population?

TRIM28 p.Ala397= (c.1191C>T) is very rare (popmax 0.00263%, nfe) (gnomAD).

TRIM28 p.Ala397=

c.1191C>T · VCV4799376

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.094	GERP -3.4, phastCons 0.54
Overall
CADD	9.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00263% European (non-Finnish) · 31/1,180,024 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00233% 34/1,461,842 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)grpmax	0.00263%	38,065

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TRIM28
Protein: p.Ala397=
Coding: c.1191C>T
MANE Select: NM_005762
Type: single nucleotide variant
Location: chr19:58548383 (GRCh38)
Gene constraint: LOEUF 0.17 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.59 · 10 PDB
Residue 397: an α-helix; a UniProt-annotated variant site (risk factor for wt7)

Full TRIM28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM28 p.Ala537Val Uncertain significance ★★ ⚠ same type
TRIM28 p.Arg412His Uncertain significance ★★ ⚠ same type
TRIM28 p.Arg706Cys Uncertain significance ★★ ⚠ same type
TRIM28 p.Arg767His Uncertain significance ★★ ⚠ same type
TRIM28 p.Arg795Cys Uncertain significance ★★ ⚠ same type
TRIM28 p.Asp231Tyr Uncertain significance ★★ ⚠ same type
TRIM28 p.Glu798Asp Uncertain significance ★★ ⚠ same type
TRIM28 p.Gly735Ala 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/trim28-p-ala397 (accessed [today's date]).

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