Is ADSL p.Pro467Arg (c.1400C>G) pathogenic?

ADSL p.Pro467Arg (c.1400C>G) is classified Conflicting classifications of pathogenicity in ADSL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-05-06). AlphaMissense: likely benign (0.2238); Very rare (popmax 8.48e-05%, nfe); Associated with ADSL-related disorder.

What condition is associated with ADSL p.Pro467Arg (c.1400C>G)?

ADSL p.Pro467Arg (c.1400C>G) is associated with ADSL-related disorder, adenylosuccinate lyase deficiency (ClinVar).

How common is ADSL p.Pro467Arg (c.1400C>G) in the general population?

ADSL p.Pro467Arg (c.1400C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ADSL p.Pro467Arg (c.1400C>G)?

AlphaMissense predicts likely benign (score 0.2238) — an in-silico prediction, not a clinical call.

ADSL p.Pro467Arg

c.1400C>G · rs1057521071 · VCV381551

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2238 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ADSL-related disorder

Computational evidence

Protein change
AlphaMissense	0.2238	likely benign
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	27.0	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 8.48e-05% European (non-Finnish) · 1/1,179,472 alleles

Overall 6.84e-05% 1/1,461,216 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: ADSL
Protein: p.Pro467Arg
Coding: c.1400C>G
MANE Select: NM_000026
dbSNP: rs1057521071
Type: single nucleotide variant
Location: chr22:40366467 (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 467: an α-helix

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

Disease context

ADSL-related disorder

Also linked: adenylosuccinate lyase deficiency

Similar variants

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
ADSL p.Arg190Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ADSL p.Arg190Ter 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-pro467arg (accessed [today's date]).

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