Is ARSB p.Phe62Tyr (c.185T>A) pathogenic?

ARSB p.Phe62Tyr (c.185T>A) is classified Conflicting classifications of pathogenicity in ARSB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-07). AlphaMissense: likely benign (0.1666); Ultra-rare (popmax 0.0698%, afr); Associated with Inborn genetic diseases.

What condition is associated with ARSB p.Phe62Tyr (c.185T>A)?

ARSB p.Phe62Tyr (c.185T>A) is associated with Inborn genetic diseases, mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Phe62Tyr (c.185T>A) in the general population?

ARSB p.Phe62Tyr (c.185T>A) is ultra-rare (popmax 0.0698%, afr) (gnomAD).

What do computational predictors say about ARSB p.Phe62Tyr (c.185T>A)?

AlphaMissense predicts likely benign (score 0.1666) — an in-silico prediction, not a clinical call.

ARSB p.Phe62Tyr

c.185T>A · rs779228581 · VCV286297

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0698%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1666	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -3, phastCons 1
Overall
CADD	19.59	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 0.0698% African / African-American · 49/70,164 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0487%

Overall 0.00324% 50/1,543,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0698%	1,432
Admixed American	0.00193%	51,878

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.Phe62Tyr
Coding: c.185T>A
MANE Select: NM_000046
dbSNP: rs779228581
Type: single nucleotide variant
Location: chr5:78985064 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 62: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 6

Similar variants

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
ARSB c.1213+6T>C 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-phe62tyr (accessed [today's date]).

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