Is ARSB p.Arg315Gln (c.944G>A) pathogenic?

ARSB p.Arg315Gln (c.944G>A) is classified Pathogenic/Likely pathogenic in ARSB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-08). AlphaMissense: ambiguous (0.5421); Very rare (popmax 0.0011%, sas); Associated with ARSB-related disorder.

What condition is associated with ARSB p.Arg315Gln (c.944G>A)?

ARSB p.Arg315Gln (c.944G>A) is associated with ARSB-related disorder, mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg315Gln (c.944G>A) in the general population?

ARSB p.Arg315Gln (c.944G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ARSB p.Arg315Gln (c.944G>A)?

AlphaMissense predicts ambiguous (score 0.5421) — an in-silico prediction, not a clinical call.

ARSB p.Arg315Gln

c.944G>A · rs727503809 · VCV166694

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

ambiguous

0.5421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

ARSB-related disorder

Computational evidence

Protein change
AlphaMissense	0.5421	ambiguous
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -9.57	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Overall
CADD	31.0	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 0.0011% South Asian · 1/91,078 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000684% 10/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	0.000593%	168,576

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg315Gln
Coding: c.944G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs727503809
Type: single nucleotide variant
Location: chr5:78885782 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

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

Disease context

ARSB-related disorder

Also linked: mucopolysaccharidosis type 6

Similar variants

ARSB p.Arg315Pro Pathogenic/Likely pathogenic ★★ same residue
ARSB p.Arg315Ter Pathogenic/Likely pathogenic ★★ same residue
ARSB p.Arg315= Likely benign ★ same residue
ARSB p.Arg315Gly Uncertain significance ★ ⚠ same residue
ARSB c.1142+1G>A Pathogenic ★★ same condition
ARSB c.1142+1G>T Pathogenic ★★ same condition
ARSB c.1142+2T>A Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1142+2T>C 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/arsb-p-arg315gln (accessed [today's date]).

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