Is GPATCH2 p.Gly414Arg (c.1240G>A) pathogenic?

GPATCH2 p.Gly414Arg (c.1240G>A) is classified Uncertain significance in GPATCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.34); Ultra-rare (popmax 0.0163%, nfe).

How common is GPATCH2 p.Gly414Arg (c.1240G>A) in the general population?

GPATCH2 p.Gly414Arg (c.1240G>A) is ultra-rare (popmax 0.0163%, nfe) (gnomAD).

What do computational predictors say about GPATCH2 p.Gly414Arg (c.1240G>A)?

AlphaMissense predicts likely benign (score 0.34) — an in-silico prediction, not a clinical call.

GPATCH2 p.Gly414Arg

c.1240G>A · rs745998416 · VCV2397624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.34 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0163%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.34	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -5.28	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 200 kb · p 0.29 · regional, not allelic
Overall
CADD	26.6	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 0.0163% European (non-Finnish) · 178/1,094,778 alleles

Filtering AF 0.0143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0123% 186/1,507,846 alleles · ultra-rare exomes 177/1,355,752 · genomes 9/152,094 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0163%	6,150
Remaining individualsnot grpmax-eligible	0.00855%	11,696
African / African-American	0.00279%	35,875
Finnishnot grpmax-eligible	0.00157%	63,498

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: GPATCH2
Protein: p.Gly414Arg
Coding: c.1240G>A
MANE Select: NM_018040
dbSNP: rs745998416
Type: single nucleotide variant
Location: chr1:217491717 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60

Full GPATCH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPATCH2 p.Ala396Val Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg126His Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg137Gln Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg159Cys Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg212Ile Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg218Lys Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg347Cys Uncertain significance ★ ⚠ same type
GPATCH2 p.Arg410Gln 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/gpatch2-p-gly414arg (accessed [today's date]).

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