Is ARSB p.Pro34Leu (c.101C>T) pathogenic?

ARSB p.Pro34Leu (c.101C>T) is classified Uncertain significance in ARSB (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.00244%, amr).

How common is ARSB p.Pro34Leu (c.101C>T) in the general population?

ARSB p.Pro34Leu (c.101C>T) is very rare (popmax 0.00244%, amr) (gnomAD).

What do computational predictors say about ARSB p.Pro34Leu (c.101C>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

ARSB p.Pro34Leu

c.101C>T · rs1753125870 · VCV1049153

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -7.52	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 -0.66	GERP -2.9
Overall
CADD	1.817	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00244% Admixed American · 1/40,934 alleles

Overall 7.66e-05% 1/1,306,194 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: ARSB
Protein: p.Pro34Leu
Coding: c.101C>T
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs1753125870
Type: single nucleotide variant
Location: chr5:78985148 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 34: the upar/ly6 domain; a β-strand; a disulfide bond

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

Similar variants

ARSB p.Pro34= Likely benign ★ same residue
ARSB c.1142+1G>A Pathogenic ★★ same type
ARSB c.1142+1G>T Pathogenic ★★ same type
ARSB c.1142+2T>A Pathogenic/Likely pathogenic ★★ same type
ARSB c.1142+2T>C Pathogenic ★★ same type
ARSB c.1143-1G>A Pathogenic/Likely pathogenic ★★ same type
ARSB c.1143-1G>C Pathogenic ★★ same type
ARSB c.1143-8T>G Pathogenic/Likely pathogenic ★★ same type

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/arsb-p-pro34leu (accessed [today's date]).

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