Is ASL p.Pro156Ser (c.466C>T) pathogenic?

ASL p.Pro156Ser (c.466C>T) is classified Uncertain significance in ASL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-30). AlphaMissense: likely pathogenic (0.7549); Absent from gnomAD v4.1.

How common is ASL p.Pro156Ser (c.466C>T) in the general population?

ASL p.Pro156Ser (c.466C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASL p.Pro156Ser (c.466C>T)?

AlphaMissense predicts likely pathogenic (score 0.7549) — an in-silico prediction, not a clinical call.

ASL p.Pro156Ser

c.466C>T · VCV4847542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7549 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7549	likely pathogenic
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -14.09	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	27.0	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.Pro156Ser
Coding: c.466C>T
MANE Select: NM_000048
Type: single nucleotide variant
Location: chr7:66086604 (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 156: a UniProt-annotated variant site (in arginsa); a β-strand

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

Similar variants

ASL p.Pro156Gln Likely pathogenic ★ same residue
ASL p.Pro156Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ASL p.Pro156= Likely benign ★ same residue
ASL c.1062+5G>C Likely pathogenic ★★ same type
ASL c.1143+1G>T Pathogenic/Likely pathogenic ★★ same type
ASL c.13-1G>C Pathogenic/Likely pathogenic ★★ same type
ASL c.291+1G>T Likely pathogenic ★★ same type
ASL c.348+1G>A Pathogenic/Likely pathogenic ★★ same type

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-pro156ser (accessed [today's date]).

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