Is ASL p.Pro156Gln (c.467C>A) pathogenic?

ASL p.Pro156Gln (c.467C>A) is classified Likely pathogenic in ASL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely pathogenic (0.9547); Very rare (popmax 0.000169%, nfe); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Pro156Gln (c.467C>A)?

ASL p.Pro156Gln (c.467C>A) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Pro156Gln (c.467C>A) in the general population?

ASL p.Pro156Gln (c.467C>A) is very rare (popmax 0.000169%, nfe) (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.Pro156Gln (c.467C>A)?

AlphaMissense predicts likely pathogenic (score 0.9547) — an in-silico prediction, not a clinical call.

ASL p.Pro156Gln

c.467C>A · rs769017508 · VCV1958571

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
AlphaMissense	0.9547	likely pathogenic ✓ concordant with ClinVar · top 10% in ASL
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -15.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.81	acceptor gain · deltas
Pangolin	Δ0.67	gain · loss 0.29 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	35.0	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 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,564 alleles · very rare

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.Pro156Gln
Coding: c.467C>A
MANE Select: NM_000048
dbSNP: rs769017508
Type: single nucleotide variant
Location: chr7:66086605 (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 156: a UniProt-annotated variant site (in arginsa); a β-strand

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.Pro156Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ASL p.Pro156= Likely benign ★ same residue
ASL p.Pro156Ser Uncertain significance ★ ⚠ 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

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-pro156gln (accessed [today's date]).

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