Is GUSB p.Val137Phe (c.409G>T) pathogenic?

GUSB p.Val137Phe (c.409G>T) is classified Uncertain significance in GUSB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). AlphaMissense: likely benign (0.1205); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GUSB p.Val137Phe (c.409G>T)?

GUSB p.Val137Phe (c.409G>T) is associated with Inborn genetic diseases (ClinVar).

How common is GUSB p.Val137Phe (c.409G>T) in the general population?

GUSB p.Val137Phe (c.409G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GUSB p.Val137Phe (c.409G>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

GUSB p.Val137Phe

c.409G>T · rs1791875511 · VCV2387030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,700)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.748	pathogenic-leaning
SaProt	LLR -6.75	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -1.8, phastCons 0.91
Regional constraint	o/e 1.01	unconstrained · MANE · 6,069 bp · p 0.83 · regional, not allelic
Overall
CADD	19.51	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

No allele count reported in gnomAD v4.1 (AN 1,599,700). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GUSB
Protein: p.Val137Phe
Coding: c.409G>T
MANE Select: NM_000181
dbSNP: rs1791875511
Type: single nucleotide variant
Location: chr7:65979899 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 137: 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.Val137= 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-val137phe (accessed [today's date]).

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