Is ARSB p.Asp54His (c.160G>C) pathogenic?

ARSB p.Asp54His (c.160G>C) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). AlphaMissense: likely pathogenic (0.9903); Very rare (popmax 8.79e-05%, nfe).

How common is ARSB p.Asp54His (c.160G>C) in the general population?

ARSB p.Asp54His (c.160G>C) is very rare (popmax 8.79e-05%, nfe) (gnomAD).

What do computational predictors say about ARSB p.Asp54His (c.160G>C)?

AlphaMissense predicts likely pathogenic (score 0.9903) — an in-silico prediction, not a clinical call.

ARSB p.Asp54His

c.160G>C · rs1554032216 · VCV2577244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.79e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9903	likely pathogenic · top 1% in ARSB
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -16.07	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 7.2	GERP 1.5, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.79e-05% European (non-Finnish) · 1/1,137,862 alleles

Overall 7.26e-05% 1/1,377,616 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.Asp54His
Coding: c.160G>C
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs1554032216
Type: single nucleotide variant
Location: chr5:78985089 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB
Residue 54: 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 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
ARSB c.1213+6T>C 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-asp54his (accessed [today's date]).

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