Is USP36 p.Pro443= (c.1329C>T) pathogenic?

USP36 p.Pro443= (c.1329C>T) is classified Benign in USP36 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-14). Low-frequency (popmax 1.58%, afr).

How common is USP36 p.Pro443= (c.1329C>T) in the general population?

USP36 p.Pro443= (c.1329C>T) is low-frequency (popmax 1.58%, afr) (gnomAD).

USP36 p.Pro443=

c.1329C>T · rs75321857 · VCV780453

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.58%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.91	GERP -4.7
Overall
CADD	1.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.58% African / African-American · 1,186/74,996 alleles

Filtering AF 1.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.48%

Overall 0.0917% 1,480/1,614,028 alleles · low-frequency exomes 764/1,461,842 · genomes 716/152,186 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	6.69%	15
African / African-Americangrpmax	1.58%	63
Remaining individualsnot grpmax-eligible	0.096%	1,042
Middle Eastern	0.0828%	1,208
Admixed American	0.0717%	1,395
European (non-Finnish)	0.0102%	9,834
South Asian	0.00439%	22,769
East Asian	0.00223%	44,868

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: USP36
Protein: p.Pro443=
Coding: c.1329C>T
MANE Select: NM_001385174
dbSNP: rs75321857
Type: single nucleotide variant
Location: chr17:78812938 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.88 · 2 PDB
Residue 443: the 'disordered' region

Full USP36 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP36 p.Arg887Pro Benign ★★ same type
USP36 p.Asn1096= Benign ★★ same type
USP36 p.Asp270= Benign ★★ same type
USP36 p.Gly444Ser Benign ★★ same type
USP36 p.His200Asn Likely benign ★★ ⚠ same type
USP36 p.Phe164= Benign/Likely benign ★★ same type
USP36 p.Pro346= Benign ★★ same type
USP36 p.Pro479Leu Benign ★★ 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/usp36-p-pro443 (accessed [today's date]).

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