Is GPATCH3 c.451+3A>G pathogenic?

GPATCH3 c.451+3A>G is classified Likely benign in GPATCH3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-11). Ultra-rare (popmax 0.0793%, nfe); Associated with GPATCH3-related disorder.

What condition is associated with GPATCH3 c.451+3A>G?

GPATCH3 c.451+3A>G is associated with GPATCH3-related disorder (ClinVar).

How common is GPATCH3 c.451+3A>G in the general population?

GPATCH3 c.451+3A>G is ultra-rare (popmax 0.0793%, nfe) (gnomAD).

GPATCH3 c.451+3A>G

rs199841851 · VCV3049452

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0793%, nfe)

Conditions

GPATCH3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +3	donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.1	GERP 1.3, phastCons 1
Non-coding constraint	Z -1.88	1 kb window · o/e 1.14 · regional · uncalibrated
Overall
CADD	16.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0793% European (non-Finnish) · 936/1,179,926 alleles

Filtering AF 0.0751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0734%

Overall 0.059% 952/1,613,984 alleles · ultra-rare exomes 905/1,461,650 · genomes 47/152,334 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0793%	1,261
Remaining individualsnot grpmax-eligible	0.0192%	5,209
African / African-American	0.00533%	18,762

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
Coding: c.451+3A>G
MANE Select: NM_022078
dbSNP: rs199841851
Type: single nucleotide variant
Location: chr1:26899989 (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

Disease context

GPATCH3-related disorder

Similar variants

GPATCH3 p.Leu460= Likely benign same condition
GPATCH3 p.Pro212= Likely benign same condition
GPATCH3 p.Pro462= Likely benign same condition
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

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-c-451-plus-3a-g (accessed [today's date]).

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