Is GUSB p.Ala413Val (c.1238C>T) pathogenic?

GUSB p.Ala413Val (c.1238C>T) is classified Conflicting classifications of pathogenicity in GUSB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1207); Very rare (popmax 0.00805%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GUSB p.Ala413Val (c.1238C>T)?

GUSB p.Ala413Val (c.1238C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Ala413Val (c.1238C>T) in the general population?

GUSB p.Ala413Val (c.1238C>T) is very rare (popmax 0.00805%, nfe) (gnomAD).

What do computational predictors say about GUSB p.Ala413Val (c.1238C>T)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

GUSB p.Ala413Val

c.1238C>T · rs752523400 · VCV908805

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -4.29	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 -5.2	GERP -3
Regional constraint	o/e 0.75	unconstrained · MANE · 15 kb · p 3.7e-08 · regional, not allelic
Overall
CADD	0.434	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 0.00805% European (non-Finnish) · 95/1,180,052 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00644% 104/1,614,002 alleles · very rare exomes 99/1,461,768 · genomes 5/152,234 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00805%	12,422
African / African-American	0.00667%	14,985
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Admixed American	0.00167%	60,006
South Asian	0.0011%	91,092

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.Ala413Val
Coding: c.1238C>T
MANE Select: NM_000181
dbSNP: rs752523400
Type: single nucleotide variant
Location: chr7:65974532 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB

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

Also linked: mucopolysaccharidosis type 7

Similar variants

GUSB p.Ala413= Likely benign ★ same residue
GUSB c.1244+1G>A Pathogenic ★★ same condition
GUSB c.581+1G>A Pathogenic/Likely pathogenic ★★ same condition
GUSB c.724+1G>T Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Ala619Val Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg110Ter Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg167Ter Pathogenic/Likely pathogenic ★★ same condition
GUSB p.Arg216Trp Pathogenic/Likely pathogenic ★★ 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-ala413val (accessed [today's date]).

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