Is ARSB p.Val48Ala (c.143T>C) pathogenic?

ARSB p.Val48Ala (c.143T>C) is classified Uncertain significance in ARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.6038); Very rare (popmax 0.00288%, afr); Associated with Inborn genetic diseases.

What condition is associated with ARSB p.Val48Ala (c.143T>C)?

ARSB p.Val48Ala (c.143T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ARSB p.Val48Ala (c.143T>C) in the general population?

ARSB p.Val48Ala (c.143T>C) is very rare (popmax 0.00288%, afr) (gnomAD).

What do computational predictors say about ARSB p.Val48Ala (c.143T>C)?

AlphaMissense predicts likely pathogenic (score 0.6038) — an in-silico prediction, not a clinical call.

ARSB p.Val48Ala

c.143T>C · VCV4149288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6038 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6038	likely pathogenic
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -12.46	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 11	GERP 1.5, phastCons 1
Overall
CADD	27.3	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 0.00288% African / African-American · 2/69,502 alleles

Filtering AF 0.000477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000179%

Overall 0.00033% 5/1,513,338 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00288%	34,751
European (non-Finnish)	0.000266%	376,354

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.Val48Ala
Coding: c.143T>C
MANE Select: NM_000046
Type: single nucleotide variant
Location: chr5:78985106 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 1 PDB
Residue 48: a β-strand

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

Similar variants

ARSB p.Val48= Likely benign ★ same residue
ARSB p.Gly324Val Pathogenic/Likely pathogenic ★★ same condition
ARSB p.Arg180His Uncertain significance ★★ ⚠ same condition
ARSB p.Asn225Lys Uncertain significance ★★ ⚠ same condition
ARSB p.Asn262Asp Uncertain significance ★★ ⚠ same condition
ARSB p.Asp416Val Uncertain significance ★★ ⚠ same condition
ARSB p.Gly309Ser Uncertain significance ★★ ⚠ same condition
ARSB p.Pro10Leu Uncertain significance ★★ ⚠ 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-val48ala (accessed [today's date]).

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