Is GPATCH11 p.Ala46Val (c.137C>T) pathogenic?

GPATCH11 p.Ala46Val (c.137C>T) is classified Uncertain significance in GPATCH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.1281); Very rare (popmax 0.00196%, amr).

How common is GPATCH11 p.Ala46Val (c.137C>T) in the general population?

GPATCH11 p.Ala46Val (c.137C>T) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about GPATCH11 p.Ala46Val (c.137C>T)?

AlphaMissense predicts likely benign (score 0.1281) — an in-silico prediction, not a clinical call.

GPATCH11 p.Ala46Val

c.137C>T · VCV4031115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1281	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.67	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 3.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,878 bp · p 0.23 · regional, not allelic
Overall
CADD	22.4	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 A68V vs ClinVar A46V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00196% Admixed American · 1/50,982 alleles

Overall 6.44e-05% 1/1,551,676 alleles · very rare exomes 1/1,399,562 · genomes 0/152,114 · 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.Ala46Val
Coding: c.137C>T
MANE Select: NM_174931
Type: single nucleotide variant
Location: chr2:37089717 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.60
Residue 68 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.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
GPATCH11 p.Asp64His 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-ala46val (accessed [today's date]).

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