Is GPATCH11 p.Ala146Ser (c.436G>T) pathogenic?

GPATCH11 p.Ala146Ser (c.436G>T) is classified Uncertain significance in GPATCH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1179); Ultra-rare (popmax 0.0467%, amr).

How common is GPATCH11 p.Ala146Ser (c.436G>T) in the general population?

GPATCH11 p.Ala146Ser (c.436G>T) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

What do computational predictors say about GPATCH11 p.Ala146Ser (c.436G>T)?

AlphaMissense predicts likely benign (score 0.1179) — an in-silico prediction, not a clinical call.

GPATCH11 p.Ala146Ser

c.436G>T · rs369659513 · VCV2400097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1179 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1179	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -7.68	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 2.7	GERP 0.8, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,878 bp · p 0.23 · regional, not allelic
Overall
CADD	16.41	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 A168S vs ClinVar A146S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0467% Admixed American · 28/59,914 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.00254% 41/1,612,752 alleles · ultra-rare exomes 37/1,460,670 · genomes 4/152,082 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0467%	2,140
Middle Eastern	0.0165%	6,078
African / African-American	0.00401%	24,959
Remaining individualsnot grpmax-eligible	0.0032%	31,202
European (non-Finnish)	0.000594%	168,460

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.Ala146Ser
Coding: c.436G>T
MANE Select: NM_174931
dbSNP: rs369659513
Type: single nucleotide variant
Location: chr2:37092023 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.60

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

Similar variants

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
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-ala146ser (accessed [today's date]).

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