Is ASL p.Leu262Pro (c.785T>C) pathogenic?

ASL p.Leu262Pro (c.785T>C) is classified Uncertain significance in ASL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-01-03). AlphaMissense: likely pathogenic (0.92); Absent from gnomAD v4.1; Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Leu262Pro (c.785T>C)?

ASL p.Leu262Pro (c.785T>C) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Leu262Pro (c.785T>C) in the general population?

ASL p.Leu262Pro (c.785T>C) is absent from gnomAD v4.1 (gnomAD).

How is Argininosuccinic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ASL p.Leu262Pro (c.785T>C)?

AlphaMissense predicts likely pathogenic (score 0.92) — an in-silico prediction, not a clinical call.

ASL p.Leu262Pro

c.785T>C · rs1554327586 · VCV555911

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.92 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
AlphaMissense	0.92	likely pathogenic
REVEL	0.965	strongly pathogenic-leaning
SaProt	LLR -15.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ASL
Protein: p.Leu262Pro
Coding: c.785T>C
MANE Select: NM_000048
dbSNP: rs1554327586
Type: single nucleotide variant
Location: chr7:66088873 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB
Residue 262: an α-helix; a UniProt-annotated variant site (in arginsa)

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

Disease context

argininosuccinic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Argininosuccinic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

ASL p.Leu262= Likely benign ★ same residue
ASL c.1062+5G>C Likely pathogenic ★★ same condition
ASL c.1143+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASL c.13-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASL c.291+1G>T Likely pathogenic ★★ same condition
ASL c.348+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASL c.349-1G>A Likely pathogenic ★★ same condition
ASL c.446+1G>A Pathogenic ★★ same condition

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/asl-p-leu262pro (accessed [today's date]).

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