Is ASL p.Arg217Gln (c.650G>A) pathogenic?

ASL p.Arg217Gln (c.650G>A) is classified Uncertain significance in ASL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.0753); Very rare (popmax 0.00223%, eas).

How common is ASL p.Arg217Gln (c.650G>A) in the general population?

ASL p.Arg217Gln (c.650G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ASL p.Arg217Gln (c.650G>A)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

ASL p.Arg217Gln

c.650G>A · VCV3340011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.453	indeterminate
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.99	GERP -1.7, phastCons 0.57
Regional constraint	o/e 0.87	unconstrained · MANE · 17 kb · p 0.00078 · regional, not allelic
Overall
CADD	17.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000996% 16/1,606,902 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
Admixed American	0.00167%	59,962
Remaining individualsnot grpmax-eligible	0.0016%	62,436
South Asian	0.0011%	91,076
European (non-Finnish)	0.00102%	98,327

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.Arg217Gln
Coding: c.650G>A
MANE Select: NM_000048
Type: single nucleotide variant
Location: chr7:66087381 (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 217: an α-helix

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

Similar variants

ASL p.Arg217Ter Pathogenic ★★ same residue
ASL p.Arg217= 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
ASL c.349-1G>A 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-arg217gln (accessed [today's date]).

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