Is UBAP1 p.Val135Ile (c.403G>A) pathogenic?

UBAP1 p.Val135Ile (c.403G>A) is classified Uncertain significance in UBAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). AlphaMissense: likely benign (0.0877); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with UBAP1 p.Val135Ile (c.403G>A)?

UBAP1 p.Val135Ile (c.403G>A) is associated with Inborn genetic diseases (ClinVar).

How common is UBAP1 p.Val135Ile (c.403G>A) in the general population?

UBAP1 p.Val135Ile (c.403G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBAP1 p.Val135Ile (c.403G>A)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

UBAP1 p.Val135Ile

c.403G>A · rs764064548 · VCV3185440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.51	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 10	GERP 0.89, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 0.0029 · regional, not allelic
Overall
CADD	20.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UBAP1
Protein: p.Val135Ile
Coding: c.403G>A
MANE Select: NM_016525
dbSNP: rs764064548
Type: single nucleotide variant
Location: chr9:34241428 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.60 · 3 PDB
Residue 135: a UniProt-annotated variant site (in spg80)

Full UBAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UBAP1 p.Glu445Lys Uncertain significance ★★ ⚠ same condition
UBAP1 c.-104C>G Uncertain significance ★ same condition
UBAP1 c.-146G>T Uncertain significance ★ same condition
UBAP1 c.-167G>A Uncertain significance ★ same condition
UBAP1 c.-167G>C Uncertain significance ★ same condition
UBAP1 c.-167G>T Uncertain significance ★ same condition
UBAP1 c.-178G>A Uncertain significance ★ same condition
UBAP1 c.-181G>T Uncertain significance ★ same condition

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/ubap1-p-val135ile (accessed [today's date]).

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