Is ASL p.Val345= (c.1035G>A) pathogenic?

ASL p.Val345= (c.1035G>A) is classified Likely benign in ASL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Ultra-rare (popmax 0.0533%, afr); Associated with argininosuccinic aciduria.

What condition is associated with ASL p.Val345= (c.1035G>A)?

ASL p.Val345= (c.1035G>A) is associated with argininosuccinic aciduria (ClinVar).

How common is ASL p.Val345= (c.1035G>A) in the general population?

ASL p.Val345= (c.1035G>A) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

How is Argininosuccinic aciduria inherited?

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

ASL p.Val345=

c.1035G>A · rs182203503 · VCV1119311

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, afr)

Conditions

argininosuccinic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.157	moderately benign-leaning
Splicing
SpliceAI	Δ0.50	donor gain · deltas
Pangolin	Δ0.22	gain · loss 0.11 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.8	GERP 1.4, phastCons 1
Overall
CADD	17.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% African / African-American · 40/75,038 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00341% 55/1,613,850 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
Admixed American	0.02%	5,000
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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.Val345=
Coding: c.1035G>A
MANE Select: NM_000048
dbSNP: rs182203503
Type: single nucleotide variant
Location: chr7:66089668 (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 345: 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 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
ASL c.446+2T>C 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-val345 (accessed [today's date]).

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