Is ADSL p.Ala136Val (c.407C>T) pathogenic?

ADSL p.Ala136Val (c.407C>T) is classified Uncertain significance in ADSL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.2562); Absent from gnomAD v4.1; Associated with adenylosuccinate lyase deficiency.

What condition is associated with ADSL p.Ala136Val (c.407C>T)?

ADSL p.Ala136Val (c.407C>T) is associated with adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Ala136Val (c.407C>T) in the general population?

ADSL p.Ala136Val (c.407C>T) is absent from gnomAD v4.1 (gnomAD).

How is Adenylosuccinate lyase deficiency inherited?

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

What do computational predictors say about ADSL p.Ala136Val (c.407C>T)?

AlphaMissense predicts likely benign (score 0.2562) — an in-silico prediction, not a clinical call.

ADSL p.Ala136Val

c.407C>T · rs1569091418 · VCV574763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2562 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

adenylosuccinate lyase deficiency

Computational evidence

Protein change
AlphaMissense	0.2562	likely benign
REVEL	0.563	indeterminate
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	23.4	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

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: ADSL
Protein: p.Ala136Val
Coding: c.407C>T
MANE Select: NM_000026
dbSNP: rs1569091418
Type: single nucleotide variant
Location: chr22:40354252 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 4 PDB
Residue 136: an α-helix

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

Disease context

adenylosuccinate lyase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adenylosuccinate lyase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ADSL p.Ala136= Conflicting classifications of pathogenicity ★ same residue
ADSL p.Ala136Thr Uncertain significance ★★ ⚠ same residue
ADSL c.1191+5G>C Pathogenic/Likely pathogenic ★★ same condition
ADSL c.402+1G>T Likely pathogenic ★★ same condition
ADSL c.482+1G>C Likely pathogenic ★★ same condition
ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Arg149Ter 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/adsl-p-ala136val (accessed [today's date]).

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