Is ARSD p.Pro19Leu (c.56C>T) pathogenic?

ARSD p.Pro19Leu (c.56C>T) is classified Likely benign in ARSD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0918); Ultra-rare (popmax 0.0148%, eas).

How common is ARSD p.Pro19Leu (c.56C>T) in the general population?

ARSD p.Pro19Leu (c.56C>T) is ultra-rare (popmax 0.0148%, eas) (gnomAD).

What do computational predictors say about ARSD p.Pro19Leu (c.56C>T)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

ARSD p.Pro19Leu

c.56C>T · VCV3432237

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -1.7
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.083 · regional, not allelic
Overall
CADD	0.028	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 0.0148% East Asian · 5/33,708 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00374%

Overall 0.000662% 8/1,208,631 alleles · ultra-rare exomes 7/1,096,814 · genomes 1/111,817 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0148%	6,742
South Asian	0.00177%	56,507
European (non-Finnish)	0.000224%	447,353

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.Pro19Leu
Coding: c.56C>T
MANE Select: NM_001669
Type: single nucleotide variant
Location: chrX:2925754 (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-pro19leu (accessed [today's date]).

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