Is ARSD p.Ala275Glu (c.824C>A) pathogenic?

ARSD p.Ala275Glu (c.824C>A) is classified Uncertain significance in ARSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.3215); Absent from gnomAD v4.1.

How common is ARSD p.Ala275Glu (c.824C>A) in the general population?

ARSD p.Ala275Glu (c.824C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSD p.Ala275Glu (c.824C>A)?

AlphaMissense predicts likely benign (score 0.3215) — an in-silico prediction, not a clinical call.

ARSD p.Ala275Glu

c.824C>A · VCV3432246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3215 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3215	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -11.59	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.26	GERP 0.41
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.083 · regional, not allelic
Overall
CADD	17.59	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARSD
Protein: p.Ala275Glu
Coding: c.824C>A
MANE Select: NM_001669
Type: single nucleotide variant
Location: chrX:2917843 (GRCh38)
Structure: AlphaFold pLDDT 92.71

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

Similar variants

ARSD p.Cys577= Benign ★★ same type
ARSD p.Gly323= Likely benign ★★ same type
ARSD p.Gly409Glu Benign ★★ same type
ARSD p.Ser224Cys Benign ★★ ⚠ same type
ARSD p.Val500Ile Benign ★★ same type
ARSD p.Ala109Thr Uncertain significance ★ ⚠ same type
ARSD p.Ala14Thr Uncertain significance ★ ⚠ same type
ARSD p.Ala194Val Uncertain significance ★ ⚠ 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/arsd-p-ala275glu (accessed [today's date]).

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