Is GPATCH4 p.Arg215Lys (c.644G>A) pathogenic?

GPATCH4 p.Arg215Lys (c.644G>A) is classified Likely benign in GPATCH4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). Ultra-rare (popmax 0.0495%, mid).

How common is GPATCH4 p.Arg215Lys (c.644G>A) in the general population?

GPATCH4 p.Arg215Lys (c.644G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

GPATCH4 p.Arg215Lys

c.644G>A · VCV4672872

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.083	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.097, phastCons 0.99
Overall
CADD	9.849	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,058 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00186% 30/1,612,484 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,019
Admixed American	0.0218%	4,592
Remaining individualsnot grpmax-eligible	0.00801%	12,486
European (non-Finnish)	0.000763%	131,093

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.Arg215Lys
Coding: c.644G>A
Type: single nucleotide variant
Location: chr1:156595697 (GRCh38)
Gene constraint: LOEUF 1.669 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.52
Residue 215: the 'disordered' region

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

Similar variants

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
GPATCH4 p.Ala316Val 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-arg215lys (accessed [today's date]).

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