Is GPATCH3 p.Pro182Leu (c.545C>T) pathogenic?

GPATCH3 p.Pro182Leu (c.545C>T) is classified Uncertain significance in GPATCH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: ambiguous (0.4801); Ultra-rare (popmax 0.024%, nfe).

How common is GPATCH3 p.Pro182Leu (c.545C>T) in the general population?

GPATCH3 p.Pro182Leu (c.545C>T) is ultra-rare (popmax 0.024%, nfe) (gnomAD).

What do computational predictors say about GPATCH3 p.Pro182Leu (c.545C>T)?

AlphaMissense predicts ambiguous (score 0.4801) — an in-silico prediction, not a clinical call.

GPATCH3 p.Pro182Leu

c.545C>T · rs149600354 · VCV2203815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4801	ambiguous
REVEL	0.143	moderately benign-leaning
SaProt	LLR -11.67	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 9,429 bp · p 0.78 · regional, not allelic
Overall
CADD	25.5	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 0.024% European (non-Finnish) · 283/1,180,014 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0207%

Overall 0.0199% 322/1,614,144 alleles · ultra-rare exomes 281/1,461,838 · genomes 41/152,306 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.024%	4,170
African / African-American	0.0227%	4,415
Finnishnot grpmax-eligible	0.0172%	5,821
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.005%	20,002
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.0011%	91,078

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.Pro182Leu
Coding: c.545C>T
MANE Select: NM_022078
dbSNP: rs149600354
Type: single nucleotide variant
Location: chr1:26897632 (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-pro182leu (accessed [today's date]).

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