Is GPATCH3 p.Pro462= (c.1386A>G) pathogenic?

GPATCH3 p.Pro462= (c.1386A>G) is classified Likely benign in GPATCH3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-03). Rare (popmax 0.301%, afr); Associated with GPATCH3-related disorder.

What condition is associated with GPATCH3 p.Pro462= (c.1386A>G)?

GPATCH3 p.Pro462= (c.1386A>G) is associated with GPATCH3-related disorder (ClinVar).

How common is GPATCH3 p.Pro462= (c.1386A>G) in the general population?

GPATCH3 p.Pro462= (c.1386A>G) is rare (popmax 0.301%, afr) (gnomAD).

GPATCH3 p.Pro462=

c.1386A>G · rs140058066 · VCV3038161

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.301%, afr)

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 -0.26	GERP 1.1, phastCons 0.42
Overall
CADD	9.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.301% African / African-American · 226/75,026 alleles

Filtering AF 0.269% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.257%

Overall 0.0154% 248/1,613,446 alleles · rare exomes 128/1,461,198 · genomes 120/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.301%	332
Remaining individualsnot grpmax-eligible	0.0192%	5,206
Middle Eastern	0.0167%	5,982
Admixed American	0.0133%	7,500
European (non-Finnish)	8.48e-05%	1,179,631

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.Pro462=
Coding: c.1386A>G
MANE Select: NM_022078
dbSNP: rs140058066
Type: single nucleotide variant
Location: chr1:26891202 (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.Leu460= Likely benign same condition
GPATCH3 p.Pro212= 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-pro462 (accessed [today's date]).

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