Is GUSB p.Arg103Trp (c.307C>T) pathogenic?

GUSB p.Arg103Trp (c.307C>T) is classified Conflicting classifications of pathogenicity in GUSB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-11). AlphaMissense: ambiguous (0.4639); Very rare (popmax 0.00223%, eas); Associated with non-immune hydrops fetalis.

What condition is associated with GUSB p.Arg103Trp (c.307C>T)?

GUSB p.Arg103Trp (c.307C>T) is associated with non-immune hydrops fetalis, mucopolysaccharidosis type 7 (ClinVar).

How common is GUSB p.Arg103Trp (c.307C>T) in the general population?

GUSB p.Arg103Trp (c.307C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about GUSB p.Arg103Trp (c.307C>T)?

AlphaMissense predicts ambiguous (score 0.4639) — an in-silico prediction, not a clinical call.

GUSB p.Arg103Trp

c.307C>T · rs786205673 · VCV190463

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

non-immune hydrops fetalis

Computational evidence

Protein change
AlphaMissense	0.4639	ambiguous
REVEL	0.684	pathogenic-leaning
SaProt	LLR -13.22	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 3	GERP 1.4, phastCons 0.47
Regional constraint	o/e 1.01	unconstrained · MANE · 6,069 bp · p 0.83 · regional, not allelic
Overall
CADD	25.7	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 · 1/44,820 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000558% 9/1,613,094 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,820
Admixed American	0.00167%	59,778
African / African-American	0.00134%	74,790
South Asian	0.0011%	90,998
European (non-Finnish)	0.000424%	235,960

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.Arg103Trp
Coding: c.307C>T
MANE Select: NM_000181
dbSNP: rs786205673
Type: single nucleotide variant
Location: chr7:65980313 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.35 · 2 PDB
Residue 103: a β-strand

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

Disease context

non-immune hydrops fetalis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 7

Similar variants

GUSB p.Arg103= 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-arg103trp (accessed [today's date]).

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