Is ASL p.Leu54= (c.162C>T) pathogenic?

ASL p.Leu54= (c.162C>T) is classified Benign/Likely benign in ASL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-25). Rare (popmax 0.233%, nfe); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Leu54= (c.162C>T)?

ASL p.Leu54= (c.162C>T) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Leu54= (c.162C>T) in the general population?

ASL p.Leu54= (c.162C>T) is rare (popmax 0.233%, nfe) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Leu54=

c.162C>T · rs140221164 · VCV383016

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.233%, nfe)

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 0.18, phastCons 0.98
Overall
CADD	8.401	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.233% European (non-Finnish) · 2,754/1,179,856 alleles

Filtering AF 0.226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.223%

Overall 0.247% 3,981/1,613,412 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.46%	68
European (non-Finnish)grpmax	0.233%	428
Remaining individualsnot grpmax-eligible	0.182%	548
South Asian	0.13%	771
Admixed American	0.0702%	1,425
Middle Eastern	0.0495%	2,021
African / African-American	0.0227%	4,413

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASL
Protein: p.Leu54=
Coding: c.162C>T
MANE Select: NM_000048
dbSNP: rs140221164
Type: single nucleotide variant
Location: chr7:66081952 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB

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.Leu54fs Pathogenic ★ 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-leu54 (accessed [today's date]).

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