Is GPATCH11 p.Gly96Ala (c.287G>C) pathogenic?

GPATCH11 p.Gly96Ala (c.287G>C) is classified Uncertain significance in GPATCH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.1324); Ultra-rare (popmax 0.0208%, nfe).

How common is GPATCH11 p.Gly96Ala (c.287G>C) in the general population?

GPATCH11 p.Gly96Ala (c.287G>C) is ultra-rare (popmax 0.0208%, nfe) (gnomAD).

What do computational predictors say about GPATCH11 p.Gly96Ala (c.287G>C)?

AlphaMissense predicts likely benign (score 0.1324) — an in-silico prediction, not a clinical call.

GPATCH11 p.Gly96Ala

c.287G>C · VCV3282066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1324 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1324	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.23	donor loss, 41 bp away · masked 0 · deltas
Pangolin	Δ0.33	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,878 bp · p 0.23 · regional, not allelic
Overall
CADD	24.2	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 G118A vs ClinVar G96A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% European (non-Finnish) · 224/1,077,682 alleles

Filtering AF 0.0185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.016% 235/1,470,206 alleles · ultra-rare exomes 221/1,318,106 · genomes 14/152,100 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0208%	4,811
Middle Eastern	0.0175%	5,728
Remaining individualsnot grpmax-eligible	0.0105%	9,546
Admixed American	0.00409%	24,466
African / African-American	0.0028%	35,741

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.Gly96Ala
Coding: c.287G>C
MANE Select: NM_174931
Type: single nucleotide variant
Location: chr2:37090681 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.60
Residue 118 UniProt numbering: the g-patch domain

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-gly96ala (accessed [today's date]).

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