Is GPATCH3 p.Gly281Glu (c.842G>A) pathogenic?

GPATCH3 p.Gly281Glu (c.842G>A) is classified Likely benign in GPATCH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely benign (0.0534); Ultra-rare (popmax 0.0683%, amr).

How common is GPATCH3 p.Gly281Glu (c.842G>A) in the general population?

GPATCH3 p.Gly281Glu (c.842G>A) is ultra-rare (popmax 0.0683%, amr) (gnomAD).

What do computational predictors say about GPATCH3 p.Gly281Glu (c.842G>A)?

AlphaMissense predicts likely benign (score 0.0534) — an in-silico prediction, not a clinical call.

GPATCH3 p.Gly281Glu

c.842G>A · VCV3521493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0534 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0683%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0534	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -3.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.2
Regional constraint	o/e 0.99	unconstrained · MANE · 9,429 bp · p 0.78 · regional, not allelic
Overall
CADD	0.019	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0683% Admixed American · 41/60,000 alleles

Filtering AF 0.0517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.0026% 42/1,614,064 alleles · ultra-rare exomes 40/1,461,874 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0683%	1,463
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Gly281Glu
Coding: c.842G>A
MANE Select: NM_022078
Type: single nucleotide variant
Location: chr1:26897335 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.01
Residue 281: the 'disordered' region

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

Similar variants

GPATCH3 p.Gly281Arg Likely benign ★ 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-gly281glu (accessed [today's date]).

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