Is UBAP2 p.Pro453Ser (c.1357C>T) pathogenic?

UBAP2 p.Pro453Ser (c.1357C>T) is classified Uncertain significance in UBAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.0803); Very rare (popmax 8.47e-05%, nfe).

How common is UBAP2 p.Pro453Ser (c.1357C>T) in the general population?

UBAP2 p.Pro453Ser (c.1357C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about UBAP2 p.Pro453Ser (c.1357C>T)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

UBAP2 p.Pro453Ser

c.1357C>T · rs1564024382 · VCV2303307

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 0.19, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 95 kb · p 0.96 · regional, not allelic
Overall
CADD	23.3	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.2e-05% 1/1,614,182 alleles · very rare exomes 1/1,461,888 · genomes 0/152,294 · joint denominator

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: UBAP2
Protein: p.Pro453Ser
Coding: c.1357C>T
MANE Select: NM_001370062
dbSNP: rs1564024382
Type: single nucleotide variant
Location: chr9:33944553 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.47
Residue 453: the 'disordered' region

Full UBAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBAP2 p.Leu667Ile Benign ★★ same type
UBAP2 p.Met762Ile Benign ★★ same type
UBAP2 p.Ala1070Thr Uncertain significance ★ ⚠ same type
UBAP2 p.Ala217Ser Uncertain significance ★ ⚠ same type
UBAP2 p.Ala305Thr Uncertain significance ★ ⚠ same type
UBAP2 p.Ala382Thr Uncertain significance ★ ⚠ same type
UBAP2 p.Ala849Val Uncertain significance ★ ⚠ same type
UBAP2 p.Ala851Val 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/ubap2-p-pro453ser (accessed [today's date]).

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