Is GPATCH3 p.Glu39Asp (c.117G>C) pathogenic?

GPATCH3 p.Glu39Asp (c.117G>C) is classified Uncertain significance in GPATCH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely benign (0.1419); Rare (popmax 0.112%, afr).

How common is GPATCH3 p.Glu39Asp (c.117G>C) in the general population?

GPATCH3 p.Glu39Asp (c.117G>C) is rare (popmax 0.112%, afr) (gnomAD).

What do computational predictors say about GPATCH3 p.Glu39Asp (c.117G>C)?

AlphaMissense predicts likely benign (score 0.1419) — an in-silico prediction, not a clinical call.

GPATCH3 p.Glu39Asp

c.117G>C · VCV4031129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1419 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1419	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.22	GERP -4.8, phastCons 0.19
Regional constraint	o/e 0.99	unconstrained · MANE · 9,429 bp · p 0.78 · regional, not allelic
Overall
CADD	5.507	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% African / African-American · 84/75,038 alleles

Filtering AF 0.0926% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0855%

Overall 0.00663% 107/1,614,052 alleles · rare exomes 56/1,461,788 · genomes 51/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	893
Finnishnot grpmax-eligible	0.0188%	5,329
Admixed American	0.005%	20,007
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.000424%	236,000

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.Glu39Asp
Coding: c.117G>C
MANE Select: NM_022078
Type: single nucleotide variant
Location: chr1:26900326 (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

Similar variants

GPATCH3 p.Glu39Lys Uncertain significance ★ ⚠ same residue
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
GPATCH3 p.Arg160Gln Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg192Gly 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-glu39asp (accessed [today's date]).

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