Is ARSD p.Ala282Asp (c.845C>A) pathogenic?

ARSD p.Ala282Asp (c.845C>A) is classified Likely benign in ARSD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-07-31). AlphaMissense: likely pathogenic (0.8798); Very rare (popmax 0.00658%, amr); Associated with ARSD-related disorder.

What condition is associated with ARSD p.Ala282Asp (c.845C>A)?

ARSD p.Ala282Asp (c.845C>A) is associated with ARSD-related disorder (ClinVar).

How common is ARSD p.Ala282Asp (c.845C>A) in the general population?

ARSD p.Ala282Asp (c.845C>A) is very rare (popmax 0.00658%, amr) (gnomAD).

What do computational predictors say about ARSD p.Ala282Asp (c.845C>A)?

AlphaMissense predicts likely pathogenic (score 0.8798) — an in-silico prediction, not a clinical call.

ARSD p.Ala282Asp

c.845C>A · rs78034736 · VCV3060761

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8798 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00658%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARSD-related disorder

Computational evidence

Protein change
AlphaMissense	0.8798	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -14.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.8	GERP 0.47, phastCons 0.31
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.083 · regional, not allelic
Overall
CADD	21.3	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 0.00658% Admixed American · 3/45,580 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000884%

Overall 0.00166% 20/1,206,998 alleles · very rare exomes 19/1,094,275 · genomes 1/112,723 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00658%	15,193
East Asian	0.00297%	33,723
South Asian	0.00177%	56,469
African / African-American	0.00174%	57,369
European (non-Finnish)	0.00157%	63,778

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: ARSD
Protein: p.Ala282Asp
Coding: c.845C>A
MANE Select: NM_001669
dbSNP: rs78034736
Type: single nucleotide variant
Location: chrX:2917822 (GRCh38)
Structure: AlphaFold pLDDT 92.71

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

Disease context

ARSD-related disorder

Similar variants

ARSD c.1000+810T>C Likely benign same condition
ARSD c.1000+882A>G Likely benign same condition
ARSD c.1000+901A>G Likely benign same condition
ARSD c.1000+929T>C Likely benign same condition
ARSD p.Cys238Phe Likely benign same condition
ARSD p.Gln318His Likely benign same condition
ARSD p.Gly175Asp Likely benign same condition
ARSD p.Gly221Ser Likely benign 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/arsd-p-ala282asp (accessed [today's date]).

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