Is TRIM63 c.159+1G>A pathogenic?

TRIM63 c.159+1G>A is classified Likely pathogenic in TRIM63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-19). Very rare (popmax 0.00934%, afr).

How common is TRIM63 c.159+1G>A in the general population?

TRIM63 c.159+1G>A is very rare (popmax 0.00934%, afr) (gnomAD).

TRIM63 c.159+1G>A

VCV4540935

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.64	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.67	loss · gain 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Non-coding constraint	Z 2.10	1 kb window · o/e 0.86 · regional · uncalibrated
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,908 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00462%

Overall 0.00514% 83/1,613,666 alleles · very rare exomes 73/1,461,508 · genomes 10/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,701
European (non-Finnish)	0.00619%	16,164
Remaining individualsnot grpmax-eligible	0.0048%	20,821

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
Coding: c.159+1G>A
MANE Select: NM_032588
Type: single nucleotide variant
Location: chr1:26067335 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88 · 3 PDB

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

Similar variants

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
TRIM63 p.Arg62Trp Uncertain significance ★★ ⚠ same type
TRIM63 p.Arg74His 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-c-159-plus-1g-a (accessed [today's date]).

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