Is ADSL p.Glu80Asp (c.240A>C) pathogenic?

ADSL p.Glu80Asp (c.240A>C) is classified Uncertain significance in ADSL (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-02). AlphaMissense: likely pathogenic (0.7517); Very rare (popmax 6.84e-05%).

How common is ADSL p.Glu80Asp (c.240A>C) in the general population?

ADSL p.Glu80Asp (c.240A>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ADSL p.Glu80Asp (c.240A>C)?

AlphaMissense predicts likely pathogenic (score 0.7517) — an in-silico prediction, not a clinical call.

ADSL p.Glu80Asp

c.240A>C · rs1064794245 · VCV420030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7517 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7517	likely pathogenic
REVEL	0.739	pathogenic-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.099	GERP -4.7, phastCons 0.011
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	18.94	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 6.84e-05%

Overall 6.84e-05% 1/1,461,688 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.Glu80Asp
Coding: c.240A>C
MANE Select: NM_000026
dbSNP: rs1064794245
Type: single nucleotide variant
Location: chr22:40349918 (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 80: an α-helix

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

Similar variants

ADSL c.1191+5G>C Pathogenic/Likely pathogenic ★★ same type
ADSL c.402+1G>T Likely pathogenic ★★ same type
ADSL c.482+1G>C Likely pathogenic ★★ same type
ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same type
ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ same type
ADSL p.Arg149Ter Pathogenic/Likely pathogenic ★★ same type
ADSL p.Arg190Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
ADSL p.Arg190Ter 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/adsl-p-glu80asp (accessed [today's date]).

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