Is ASL p.Lys69= (c.207G>A) pathogenic?

ASL p.Lys69= (c.207G>A) is classified Uncertain significance in ASL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-01-27). Absent from gnomAD v4.1; Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Lys69= (c.207G>A)?

ASL p.Lys69= (c.207G>A) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Lys69= (c.207G>A) in the general population?

ASL p.Lys69= (c.207G>A) 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.

ASL p.Lys69=

c.207G>A · rs886043007 · VCV285041

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,136)

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	donor loss · deltas
Pangolin	Δ0.38	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,602,136). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ASL
Protein: p.Lys69=
Coding: c.207G>A
MANE Select: NM_000048
dbSNP: rs886043007
Type: single nucleotide variant
Location: chr7:66081997 (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 69: a modified residue (n6-acetyllysine); an α-helix

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.Lys69Arg Likely 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-lys69 (accessed [today's date]).

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