Is UBAP1 p.Ala412Val (c.1235C>T) pathogenic?

UBAP1 p.Ala412Val (c.1235C>T) is classified Uncertain significance in UBAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: ambiguous (0.5199); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with UBAP1 p.Ala412Val (c.1235C>T)?

UBAP1 p.Ala412Val (c.1235C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBAP1 p.Ala412Val (c.1235C>T) in the general population?

UBAP1 p.Ala412Val (c.1235C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about UBAP1 p.Ala412Val (c.1235C>T)?

AlphaMissense predicts ambiguous (score 0.5199) — an in-silico prediction, not a clinical call.

UBAP1 p.Ala412Val

c.1235C>T · VCV3464987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5199	ambiguous
REVEL	0.506	indeterminate
SaProt	LLR -11.75	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 9,962 bp · p 0.0098 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.2e-05% 1/1,614,168 alleles · very rare exomes 1/1,461,878 · genomes 0/152,290 · 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: UBAP1
Protein: p.Ala412Val
Coding: c.1235C>T
MANE Select: NM_016525
Type: single nucleotide variant
Location: chr9:34249930 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.60 · 3 PDB
Residue 412: a UniProt-annotated variant site (in spg80); a UniProt-annotated variant site (in spg80; uncertain significance); the uba 1 domain; an α-helix

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-ala412val (accessed [today's date]).

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