Is TRIM63 p.Glu208= (c.624G>A) pathogenic?

TRIM63 p.Glu208= (c.624G>A) is classified Likely benign in TRIM63 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-09). Ultra-rare (popmax 0.0512%, eas); Associated with TRIM63-related disorder.

What condition is associated with TRIM63 p.Glu208= (c.624G>A)?

TRIM63 p.Glu208= (c.624G>A) is associated with TRIM63-related disorder (ClinVar).

How common is TRIM63 p.Glu208= (c.624G>A) in the general population?

TRIM63 p.Glu208= (c.624G>A) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

TRIM63 p.Glu208=

c.624G>A · rs183036213 · VCV3057405

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, eas)

Conditions

TRIM63-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.008	GERP -1.2, phastCons 0.004
Overall
CADD	6.774	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% East Asian · 23/44,892 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00421% 68/1,614,188 alleles · ultra-rare exomes 63/1,461,862 · genomes 5/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,952
South Asian	0.0329%	3,036
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00167%	60,024
European (non-Finnish)	0.000339%	295,009

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: TRIM63
Protein: p.Glu208=
Coding: c.624G>A
MANE Select: NM_032588
dbSNP: rs183036213
Type: single nucleotide variant
Location: chr1:26058597 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB
Residue 208: the 'interaction with ttn' region

Full TRIM63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TRIM63-related disorder

Similar variants

TRIM63 c.831+2T>G Uncertain significance ★ same condition
TRIM63 p.Pro140= Likely benign same condition
TRIM63 p.Ala244Val Uncertain significance ★★ ⚠ same type
TRIM63 p.Ala289Val Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg112Gln Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg183His Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg230Trp Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg62Gln 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/trim63-p-glu208 (accessed [today's date]).

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