Is USP19 p.Pro437= (c.1311G>A) pathogenic?

USP19 p.Pro437= (c.1311G>A) is classified Likely benign in USP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-09). Ultra-rare (popmax 0.0657%, mid).

How common is USP19 p.Pro437= (c.1311G>A) in the general population?

USP19 p.Pro437= (c.1311G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

USP19 p.Pro437=

c.1311G>A · rs201580030 · VCV745893

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.7	GERP -5.2
Overall
CADD	1.089	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.0542% 875/1,613,890 alleles · ultra-rare exomes 806/1,461,744 · genomes 69/152,146 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.185%	542
Middle Easterngrpmax	0.0657%	1,521
South Asian	0.0637%	1,570
European (non-Finnish)	0.0549%	1,821
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.016%	6,243
Admixed American	0.0133%	7,501
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
East Asian	0.00223%	44,882

Finnish 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: USP19
Protein: p.Pro437=
Coding: c.1311G>A
MANE Select: NM_001199161
dbSNP: rs201580030
Type: single nucleotide variant
Location: chr3:49116324 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.32 · 5 PDB
Residue 437: the 'disordered' region

Full USP19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP19 p.Pro437Leu Uncertain significance ★ ⚠ same residue
USP19 c.2292+7T>C Benign ★★ same type
USP19 p.Pro487= Benign ★★ same type
USP19 c.4039-440G>A Uncertain significance ★ ⚠ same type
USP19 c.4039-477G>A Uncertain significance ★ ⚠ same type
USP19 c.4039-482C>G Uncertain significance ★ ⚠ same type
USP19 c.4039-518G>A Uncertain significance ★ ⚠ same type
USP19 c.4039-519C>T 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/usp19-p-pro437 (accessed [today's date]).

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