Is ARSD p.Val540Met (c.1618G>A) pathogenic?

ARSD p.Val540Met (c.1618G>A) is classified Uncertain significance in ARSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely benign (0.2835); Very rare (popmax 0.00514%, nfe).

How common is ARSD p.Val540Met (c.1618G>A) in the general population?

ARSD p.Val540Met (c.1618G>A) is very rare (popmax 0.00514%, nfe) (gnomAD).

What do computational predictors say about ARSD p.Val540Met (c.1618G>A)?

AlphaMissense predicts likely benign (score 0.2835) — an in-silico prediction, not a clinical call.

ARSD p.Val540Met

c.1618G>A · VCV3949144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00514%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2835	likely benign
REVEL	0.416	indeterminate
SaProt	LLR -12.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.4, phastCons 0.45
Regional constraint	o/e 0.90	unconstrained · MANE · 2,698 bp · p 0.17 · regional, not allelic
Overall
CADD	19.68	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 0.00514% European (non-Finnish) · 46/895,172 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00352%

Overall 0.00413% 50/1,210,278 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00514%	19,460
Remaining individualsnot grpmax-eligible	0.0042%	23,791
South Asian	0.00176%	56,702
African / African-American	0.00174%	57,448

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.Val540Met
Coding: c.1618G>A
MANE Select: NM_001669
Type: single nucleotide variant
Location: chrX:2907435 (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-val540met (accessed [today's date]).

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