Is USP19 p.Ser345Phe (c.1034C>T) pathogenic?

USP19 p.Ser345Phe (c.1034C>T) is classified Uncertain significance in USP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely benign (0.1313); Very rare (popmax 0.00267%, afr).

How common is USP19 p.Ser345Phe (c.1034C>T) in the general population?

USP19 p.Ser345Phe (c.1034C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about USP19 p.Ser345Phe (c.1034C>T)?

AlphaMissense predicts likely benign (score 0.1313) — an in-silico prediction, not a clinical call.

USP19 p.Ser345Phe

c.1034C>T · rs778762747 · VCV2223129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1313 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1313	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,407 bp · p 0.42 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S244F vs ClinVar S345F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,870 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,435
European (non-Finnish)	0.000763%	131,116

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.Ser345Phe
Coding: c.1034C>T
MANE Select: NM_001199161
dbSNP: rs778762747
Type: single nucleotide variant
Location: chr3:49116819 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.32 · 5 PDB
Residue 244 UniProt numbering: a modified residue (phosphoserine); the 'disordered' region

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

Similar variants

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
USP19 c.4039-543A>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-ser345phe (accessed [today's date]).

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