Is GPATCH2 p.Ile356Val (c.1066A>G) pathogenic?

GPATCH2 p.Ile356Val (c.1066A>G) is classified Uncertain significance in GPATCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0671); Ultra-rare (popmax 0.0294%, afr).

How common is GPATCH2 p.Ile356Val (c.1066A>G) in the general population?

GPATCH2 p.Ile356Val (c.1066A>G) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about GPATCH2 p.Ile356Val (c.1066A>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

GPATCH2 p.Ile356Val

c.1066A>G · rs369527117 · VCV2462459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.75	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 0.52	GERP 0.2, phastCons 0.8
Regional constraint	o/e 0.96	unconstrained · MANE · 200 kb · p 0.29 · regional, not allelic
Overall
CADD	14.98	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 0.0294% African / African-American · 22/74,816 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.00175% 28/1,604,540 alleles · ultra-rare exomes 10/1,452,212 · genomes 18/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0294%	3,401
Admixed American	0.00501%	19,949
Remaining individualsnot grpmax-eligible	0.00322%	31,087
South Asian	0.0011%	90,592

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.Ile356Val
Coding: c.1066A>G
MANE Select: NM_018040
dbSNP: rs369527117
Type: single nucleotide variant
Location: chr1:217610353 (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-ile356val (accessed [today's date]).

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