Is GPATCH3 p.Leu460= (c.1380A>G) pathogenic?

GPATCH3 p.Leu460= (c.1380A>G) is classified Likely benign in GPATCH3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-28). Rare (popmax 0.313%, nfe); Associated with GPATCH3-related disorder.

What condition is associated with GPATCH3 p.Leu460= (c.1380A>G)?

GPATCH3 p.Leu460= (c.1380A>G) is associated with GPATCH3-related disorder (ClinVar).

How common is GPATCH3 p.Leu460= (c.1380A>G) in the general population?

GPATCH3 p.Leu460= (c.1380A>G) is rare (popmax 0.313%, nfe) (gnomAD).

GPATCH3 p.Leu460=

c.1380A>G · rs35647061 · VCV3044306

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.313%, nfe)

Conditions

GPATCH3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -4.3
Overall
CADD	0.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.313% European (non-Finnish) · 3,696/1,179,576 alleles

Filtering AF 0.305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.301%

Overall 0.258% 4,160/1,613,314 alleles · rare exomes 3,961/1,461,020 · genomes 199/152,294 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.313%	319
Remaining individualsnot grpmax-eligible	0.311%	322
South Asian	0.189%	529
Admixed American	0.105%	952
Middle Eastern	0.101%	994
African / African-American	0.036%	2,779
Finnishnot grpmax-eligible	0.00313%	31,951

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: GPATCH3
Protein: p.Leu460=
Coding: c.1380A>G
MANE Select: NM_022078
dbSNP: rs35647061
Type: single nucleotide variant
Location: chr1:26891208 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.01

Full GPATCH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GPATCH3-related disorder

Similar variants

GPATCH3 c.451+3A>G Likely benign same condition
GPATCH3 p.Pro212= Likely benign same condition
GPATCH3 p.Pro462= Likely benign same condition
GPATCH3 p.Ala254Thr Uncertain significance ★ ⚠ same type
GPATCH3 p.Ala27Ser Uncertain significance ★ ⚠ same type
GPATCH3 p.Ala342Val Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg109Lys Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg124Cys 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/gpatch3-p-leu460 (accessed [today's date]).

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