Is ARSD p.Val508Met (c.1522G>A) pathogenic?

ARSD p.Val508Met (c.1522G>A) is classified Uncertain significance in ARSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.3351); Very rare (popmax 0.00913%, eas).

How common is ARSD p.Val508Met (c.1522G>A) in the general population?

ARSD p.Val508Met (c.1522G>A) is very rare (popmax 0.00913%, eas) (gnomAD).

What do computational predictors say about ARSD p.Val508Met (c.1522G>A)?

AlphaMissense predicts likely benign (score 0.3351) — an in-silico prediction, not a clinical call.

ARSD p.Val508Met

c.1522G>A · VCV3949204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3351 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00913%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3351	likely benign
REVEL	0.577	indeterminate
SaProt	LLR -9.27	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 2.4	GERP 0.4, phastCons 0.96
Regional constraint	o/e 0.90	unconstrained · MANE · 2,698 bp · p 0.17 · regional, not allelic
Overall
CADD	19.95	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00913% East Asian · 3/32,873 alleles

Filtering AF 0.00242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00127%

Overall 0.00076% 9/1,183,650 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00913%	10,958
Remaining individualsnot grpmax-eligible	0.00216%	46,367
South Asian	0.0019%	52,572
European (non-Finnish)	0.000454%	220,240

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.Val508Met
Coding: c.1522G>A
MANE Select: NM_001669
Type: single nucleotide variant
Location: chrX:2907531 (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-val508met (accessed [today's date]).

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