Is GPATCH3 p.Arg214Trp (c.640C>T) pathogenic?

GPATCH3 p.Arg214Trp (c.640C>T) is classified Uncertain significance in GPATCH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1555); Ultra-rare (popmax 0.0367%, amr).

How common is GPATCH3 p.Arg214Trp (c.640C>T) in the general population?

GPATCH3 p.Arg214Trp (c.640C>T) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

What do computational predictors say about GPATCH3 p.Arg214Trp (c.640C>T)?

AlphaMissense predicts likely benign (score 0.1555) — an in-silico prediction, not a clinical call.

GPATCH3 p.Arg214Trp

c.640C>T · rs762217780 · VCV3101172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1555	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP -0.11, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 9,429 bp · p 0.78 · regional, not allelic
Overall
CADD	24.7	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 0.0367% Admixed American · 22/59,988 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00347% 56/1,614,074 alleles · ultra-rare exomes 39/1,461,888 · genomes 17/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,727
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.004%	24,975
European (non-Finnish)	0.00186%	53,638

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.Arg214Trp
Coding: c.640C>T
MANE Select: NM_022078
dbSNP: rs762217780
Type: single nucleotide variant
Location: chr1:26897537 (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-arg214trp (accessed [today's date]).

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