Is GUSB p.Ala151Asp (c.452C>A) pathogenic?

GUSB p.Ala151Asp (c.452C>A) is classified Uncertain significance in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: ambiguous (0.445); Very rare (popmax 0.00934%, afr); Associated with Inborn genetic diseases.

What condition is associated with GUSB p.Ala151Asp (c.452C>A)?

GUSB p.Ala151Asp (c.452C>A) is associated with Inborn genetic diseases (ClinVar).

How common is GUSB p.Ala151Asp (c.452C>A) in the general population?

GUSB p.Ala151Asp (c.452C>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about GUSB p.Ala151Asp (c.452C>A)?

AlphaMissense predicts ambiguous (score 0.445) — an in-silico prediction, not a clinical call.

GUSB p.Ala151Asp

c.452C>A · VCV4621241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.445 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.445	ambiguous
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -11.54	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -2.8, phastCons 0.98
Regional constraint	o/e 1.01	unconstrained · MANE · 6,069 bp · p 0.83 · regional, not allelic
Overall
CADD	19.27	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 0.00934% African / African-American · 7/74,910 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,194 alleles · very rare

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: GUSB
Protein: p.Ala151Asp
Coding: c.452C>A
MANE Select: NM_000181
Type: single nucleotide variant
Location: chr7:65979856 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 151: a β-strand

Full GUSB 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

GUSB p.Ala151= Likely benign ★ same residue
GUSB p.Ala380Thr Uncertain significance ★★ ⚠ same condition
GUSB p.Arg116His Uncertain significance ★★ ⚠ same condition
GUSB p.Arg57Gly Uncertain significance ★★ ⚠ same condition
GUSB p.Asn254His Uncertain significance ★★ ⚠ same condition
GUSB p.His509Gln Uncertain significance ★★ ⚠ same condition
GUSB p.Lys606Glu Uncertain significance ★★ ⚠ same condition
GUSB p.Pro178Thr 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/gusb-p-ala151asp (accessed [today's date]).

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