Is GPATCH3 p.Gln35Arg (c.104A>G) pathogenic?

GPATCH3 p.Gln35Arg (c.104A>G) is classified Uncertain significance in GPATCH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: ambiguous (0.3544); Rare (popmax 0.232%, afr).

How common is GPATCH3 p.Gln35Arg (c.104A>G) in the general population?

GPATCH3 p.Gln35Arg (c.104A>G) is rare (popmax 0.232%, afr) (gnomAD).

What do computational predictors say about GPATCH3 p.Gln35Arg (c.104A>G)?

AlphaMissense predicts ambiguous (score 0.3544) — an in-silico prediction, not a clinical call.

GPATCH3 p.Gln35Arg

c.104A>G · rs138822408 · VCV2217802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3544 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.232%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3544	ambiguous
REVEL	0.268	benign-leaning
SaProt	LLR -5.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 9,429 bp · p 0.78 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.232% African / African-American · 174/75,048 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.193%

Overall 0.012% 193/1,614,086 alleles · rare exomes 102/1,461,804 · genomes 91/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.232%	431
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00333%	30,011
South Asian	0.0011%	91,080
European (non-Finnish)	0.000254%	393,348

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: GPATCH3
Protein: p.Gln35Arg
Coding: c.104A>G
MANE Select: NM_022078
dbSNP: rs138822408
Type: single nucleotide variant
Location: chr1:26900339 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.01

Full GPATCH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPATCH3 p.Ala254Thr Uncertain significance ★ ⚠ same type
GPATCH3 p.Ala27Ser Uncertain significance ★ ⚠ same type
GPATCH3 p.Ala342Val Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg109Lys Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg124Cys Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg160Gln Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg192Gly Uncertain significance ★ ⚠ same type
GPATCH3 p.Arg200Gln 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/gpatch3-p-gln35arg (accessed [today's date]).

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