Is ARSB p.Pro116Leu (c.347C>T) pathogenic?

ARSB p.Pro116Leu (c.347C>T) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-26). AlphaMissense: ambiguous (0.5058); Very rare (popmax 0.00133%, afr).

How common is ARSB p.Pro116Leu (c.347C>T) in the general population?

ARSB p.Pro116Leu (c.347C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ARSB p.Pro116Leu (c.347C>T)?

AlphaMissense predicts ambiguous (score 0.5058) — an in-silico prediction, not a clinical call.

ARSB p.Pro116Leu

c.347C>T · VCV4970869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.5058	ambiguous
REVEL	0.603	indeterminate
SaProt	LLR -11.32	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.53, phastCons 1
Overall
CADD	24.0	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 0.00133% African / African-American · 1/75,004 alleles

Overall 6.84e-05% 1/1,461,884 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.Pro116Leu
Coding: c.347C>T
MANE Select: NM_020427 · reported on NM_000046
Type: single nucleotide variant
Location: chr5:78969158 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

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

Similar variants

ARSB p.Pro116His Uncertain significance ★ ⚠ 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-pro116leu (accessed [today's date]).

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