Is GPATCH2 p.Trp305Arg (c.913T>A) pathogenic?

GPATCH2 p.Trp305Arg (c.913T>A) is classified Uncertain significance in GPATCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely pathogenic (0.9881); Very rare (popmax 0.00401%, afr).

How common is GPATCH2 p.Trp305Arg (c.913T>A) in the general population?

GPATCH2 p.Trp305Arg (c.913T>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about GPATCH2 p.Trp305Arg (c.913T>A)?

AlphaMissense predicts likely pathogenic (score 0.9881) — an in-silico prediction, not a clinical call.

GPATCH2 p.Trp305Arg

c.913T>A · rs747716956 · VCV2531531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9881	likely pathogenic · top 3% in GPATCH2
REVEL	0.532	indeterminate
SaProt	LLR -10.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 200 kb · p 0.29 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00401% African / African-American · 3/74,802 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,226 alleles · very rare exomes 2/1,461,336 · genomes 2/151,890 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,934
Admixed American	0.00167%	59,924

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.Trp305Arg
Coding: c.913T>A
MANE Select: NM_018040
dbSNP: rs747716956
Type: single nucleotide variant
Location: chr1:217610994 (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-trp305arg (accessed [today's date]).

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