Is ASL p.Leu136Pro (c.407T>C) pathogenic?

ASL p.Leu136Pro (c.407T>C) is classified Uncertain significance in ASL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely pathogenic (0.8996); Absent from gnomAD v4.1; Associated with ASL-related disorder.

What condition is associated with ASL p.Leu136Pro (c.407T>C)?

ASL p.Leu136Pro (c.407T>C) is associated with ASL-related disorder (ClinVar).

How common is ASL p.Leu136Pro (c.407T>C) in the general population?

ASL p.Leu136Pro (c.407T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASL p.Leu136Pro (c.407T>C)?

AlphaMissense predicts likely pathogenic (score 0.8996) — an in-silico prediction, not a clinical call.

ASL p.Leu136Pro

c.407T>C · rs2484998290 · VCV3032644

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ASL-related disorder

Computational evidence

Protein change
AlphaMissense	0.8996	likely pathogenic
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -15.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: ASL
Protein: p.Leu136Pro
Coding: c.407T>C
MANE Select: NM_000048
dbSNP: rs2484998290
Type: single nucleotide variant
Location: chr7:66083135 (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 136: an α-helix

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

Disease context

ASL-related disorder

Similar variants

ASL p.Leu136= Likely benign ★ same residue
ASL p.Arg12Gln Pathogenic/Likely pathogenic ★★ same condition
ASL p.Arg146Trp Pathogenic/Likely pathogenic ★★ same condition
ASL p.Arg182Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ASL p.Arg182Ter Pathogenic ★★ same condition
ASL p.Arg217Ter Pathogenic ★★ same condition
ASL p.Arg379Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ASL p.Arg385Cys 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-leu136pro (accessed [today's date]).

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