Is GPATCH4 p.Arg167His (c.500G>A) pathogenic?

GPATCH4 p.Arg167His (c.500G>A) is classified Uncertain significance in GPATCH4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). Ultra-rare (popmax 0.0467%, amr).

How common is GPATCH4 p.Arg167His (c.500G>A) in the general population?

GPATCH4 p.Arg167His (c.500G>A) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

GPATCH4 p.Arg167His

c.500G>A · VCV4031135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.103	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0467% Admixed American · 23/49,268 alleles

Filtering AF 0.0319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.027%

Overall 0.0105% 162/1,540,534 alleles · ultra-rare exomes 144/1,388,252 · genomes 18/152,282 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.168%	596
Admixed Americangrpmax	0.0467%	2,142
Remaining individualsnot grpmax-eligible	0.0285%	3,504
South Asian	0.0229%	4,364
Middle Eastern	0.0212%	4,722
European (non-Finnish)	0.00503%	19,885
East Asian	0.00225%	44,478
Finnishnot grpmax-eligible	0.00192%	52,034
African / African-American	0.00138%	72,618

Ashkenazi Jewish 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: GPATCH4
Protein: p.Arg167His
Coding: c.500G>A
Type: single nucleotide variant
Location: chr1:156595841 (GRCh38)
Gene constraint: LOEUF 1.669 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.52

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

Similar variants

GPATCH4 p.Met167Lys 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-arg167his (accessed [today's date]).

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