Is ARSD p.Ala48Val (c.143C>T) pathogenic?

ARSD p.Ala48Val (c.143C>T) is classified Uncertain significance in ARSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.2054); Ultra-rare (popmax 0.0461%, amr).

How common is ARSD p.Ala48Val (c.143C>T) in the general population?

ARSD p.Ala48Val (c.143C>T) is ultra-rare (popmax 0.0461%, amr) (gnomAD).

What do computational predictors say about ARSD p.Ala48Val (c.143C>T)?

AlphaMissense predicts likely benign (score 0.2054) — an in-silico prediction, not a clinical call.

ARSD p.Ala48Val

c.143C>T · VCV3316460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2054 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2054	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.083 · regional, not allelic
Overall
CADD	14.68	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 0.0461% Admixed American · 21/45,554 alleles

Filtering AF 0.0308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0259%

Overall 0.00215% 26/1,207,376 alleles · ultra-rare exomes 23/1,096,189 · genomes 3/111,187 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0461%	2,169
East Asian	0.00296%	33,733
European (non-Finnish)	0.000448%	223,393

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.Ala48Val
Coding: c.143C>T
MANE Select: NM_001669
Type: single nucleotide variant
Location: chrX:2925667 (GRCh38)
Structure: AlphaFold pLDDT 92.71

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

Similar variants

ARSD p.Ala48Thr Uncertain significance ★ ⚠ same residue
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

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-ala48val (accessed [today's date]).

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