Is GPATCH11 p.Glu45Lys (c.133G>A) pathogenic?

GPATCH11 p.Glu45Lys (c.133G>A) is classified Uncertain significance in GPATCH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1372); Very rare (popmax 8.72e-05%, nfe).

How common is GPATCH11 p.Glu45Lys (c.133G>A) in the general population?

GPATCH11 p.Glu45Lys (c.133G>A) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about GPATCH11 p.Glu45Lys (c.133G>A)?

AlphaMissense predicts likely benign (score 0.1372) — an in-silico prediction, not a clinical call.

GPATCH11 p.Glu45Lys

c.133G>A · VCV4836671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1372 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1372	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.20	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 8.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,878 bp · p 0.23 · regional, not allelic
Overall
CADD	23.7	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E67K vs ClinVar E45K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,147,040 alleles

Overall 6.44e-05% 1/1,551,800 alleles · very rare exomes 1/1,399,534 · genomes 0/152,266 · joint denominator

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: GPATCH11
Protein: p.Glu45Lys
Coding: c.133G>A
MANE Select: NM_174931
Type: single nucleotide variant
Location: chr2:37089713 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.60
Residue 67 UniProt numbering: the 'disordered' region

Full GPATCH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPATCH11 p.Ala146Ser Uncertain significance ★ ⚠ same type
GPATCH11 p.Ala36Val Uncertain significance ★ ⚠ same type
GPATCH11 p.Ala46Val Uncertain significance ★ ⚠ same type
GPATCH11 p.Arg152Gln Uncertain significance ★ ⚠ same type
GPATCH11 p.Asn75Lys Uncertain significance ★ ⚠ same type
GPATCH11 p.Asp10Glu Uncertain significance ★ ⚠ same type
GPATCH11 p.Asp177Gly Uncertain significance ★ ⚠ same type
GPATCH11 p.Asp208Glu 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/gpatch11-p-glu45lys (accessed [today's date]).

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