Is GPATCH4 p.Thr54Ile (c.161C>T) pathogenic?

GPATCH4 p.Thr54Ile (c.161C>T) is classified Uncertain significance in GPATCH4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). Very rare (popmax 0.00119%, nfe).

How common is GPATCH4 p.Thr54Ile (c.161C>T) in the general population?

GPATCH4 p.Thr54Ile (c.161C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

GPATCH4 p.Thr54Ile

c.161C>T · VCV3282080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.221	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.38, phastCons 1
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,842 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,682 alleles · very rare

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: GPATCH4
Protein: p.Thr54Ile
Coding: c.161C>T
Type: single nucleotide variant
Location: chr1:156598428 (GRCh38)
Gene constraint: LOEUF 1.669 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.52
Residue 54: the g-patch domain

Full GPATCH4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPATCH4 p.His54Arg Uncertain significance ★ same residue
GPATCH4 c.348+115G>A Uncertain significance ★ same type
GPATCH4 c.-65A>C Uncertain significance ★ same type
GPATCH4 c.-74G>C Uncertain significance ★ same type
GPATCH4 c.-79G>C Uncertain significance ★ same type
GPATCH4 p.Ala162Thr Uncertain significance ★ same type
GPATCH4 p.Ala174Pro Uncertain significance ★ same type
GPATCH4 p.Ala219Val 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/gpatch4-p-thr54ile (accessed [today's date]).

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