Is ASL p.Pro208Ser (c.622C>T) pathogenic?

ASL p.Pro208Ser (c.622C>T) is classified Uncertain significance in ASL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely benign (0.2533); Very rare (popmax 8.48e-05%, nfe); Associated with ASL-related disorder.

What condition is associated with ASL p.Pro208Ser (c.622C>T)?

ASL p.Pro208Ser (c.622C>T) is associated with ASL-related disorder (ClinVar).

How common is ASL p.Pro208Ser (c.622C>T) in the general population?

ASL p.Pro208Ser (c.622C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ASL p.Pro208Ser (c.622C>T)?

AlphaMissense predicts likely benign (score 0.2533) — an in-silico prediction, not a clinical call.

ASL p.Pro208Ser

c.622C>T · VCV3347046

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2533 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ASL-related disorder

Computational evidence

Protein change
AlphaMissense	0.2533	likely benign
REVEL	0.879	moderately pathogenic-leaning
SaProt	LLR -9.93	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, 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

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) · 1/1,179,892 alleles

Overall 6.88e-05% 1/1,454,100 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: ASL
Protein: p.Pro208Ser
Coding: c.622C>T
MANE Select: NM_000048
Type: single nucleotide variant
Location: chr7:66087353 (GRCh38)
Gene constraint: LOEUF 0.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.51 · 2 PDB

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

Disease context

ASL-related disorder

Similar variants

ASL p.Pro208Arg Likely pathogenic ★★ same residue
ASL p.Pro208Thr Likely pathogenic ★ ⚠ 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

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-pro208ser (accessed [today's date]).

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