Is ARSB p.Tyr210Cys (c.629A>G) pathogenic?

ARSB p.Tyr210Cys (c.629A>G) is classified Pathogenic in ARSB (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-14). AlphaMissense: likely pathogenic (0.8203); Ultra-rare (popmax 0.0281%, nfe); Associated with ARSB-related disorder.

What condition is associated with ARSB p.Tyr210Cys (c.629A>G)?

ARSB p.Tyr210Cys (c.629A>G) is associated with ARSB-related disorder, mucopolysaccharidosis type 6, metachromatic leukodystrophy (ClinVar).

How common is ARSB p.Tyr210Cys (c.629A>G) in the general population?

ARSB p.Tyr210Cys (c.629A>G) is ultra-rare (popmax 0.0281%, nfe) (gnomAD).

What do computational predictors say about ARSB p.Tyr210Cys (c.629A>G)?

AlphaMissense predicts likely pathogenic (score 0.8203) — an in-silico prediction, not a clinical call.

ARSB p.Tyr210Cys

c.629A>G · rs118203943 · VCV885

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely pathogenic

0.8203 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARSB-related disorder

Computational evidence

Protein change
AlphaMissense	0.8203	likely pathogenic ✓ concordant with ClinVar
REVEL	0.968	strongly pathogenic-leaning
SaProt	LLR -14.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Overall
CADD	29.3	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 0.0281% European (non-Finnish) · 332/1,179,918 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.0221% 356/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0281%	3,554
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Finnishnot grpmax-eligible	0.0125%	8,004
African / African-American	0.004%	24,977
Admixed American	0.00167%	60,016

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.Tyr210Cys
Coding: c.629A>G
MANE Select: NM_000046
dbSNP: rs118203943
Type: single nucleotide variant
Location: chr5:78964477 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 210: a disulfide bond; a UniProt-annotated variant site (in mps6; mild/intermediate)

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

Disease context

ARSB-related disorder

Also linked: mucopolysaccharidosis type 6 metachromatic leukodystrophy

Similar variants

ARSB p.Tyr210His Likely pathogenic ★ 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
ARSB c.1143-1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1143-1G>C Pathogenic ★★ same condition
ARSB c.1143-8T>G 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/arsb-p-tyr210cys (accessed [today's date]).

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