Is ASAH1 p.Glu99Asp (c.297A>C) pathogenic?

ASAH1 p.Glu99Asp (c.297A>C) is classified Uncertain significance in ASAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-15). AlphaMissense: likely benign (0.1226); Absent from gnomAD v4.1.

How common is ASAH1 p.Glu99Asp (c.297A>C) in the general population?

ASAH1 p.Glu99Asp (c.297A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASAH1 p.Glu99Asp (c.297A>C)?

AlphaMissense predicts likely benign (score 0.1226) — an in-silico prediction, not a clinical call.

ASAH1 p.Glu99Asp

c.297A>C · rs1177344121 · VCV1525154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1226 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1226	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -3.4, phastCons 0.98
Regional constraint	o/e 1.37	unconstrained · MANE · 27 kb · p 6.4e-16 · regional, not allelic
Overall
CADD	13.17	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

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: ASAH1
Protein: p.Glu99Asp
Coding: c.297A>C
MANE Select: NM_177924
dbSNP: rs1177344121
Type: single nucleotide variant
Location: chr8:18069798 (GRCh38)
Gene constraint: LOEUF 1.435 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.97 · 2 PDB
Residue 99: a disulfide bond; an α-helix

Full ASAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAH1 c.1098+1G>T Pathogenic/Likely pathogenic ★★ same type
ASAH1 c.125+1G>A Pathogenic ★★ same type
ASAH1 c.457+4A>G Pathogenic/Likely pathogenic ★★ same type
ASAH1 c.648+1G>C Likely pathogenic ★★ same type
ASAH1 c.786-2A>G Likely pathogenic ★★ same type
ASAH1 p.Arg254Gly Pathogenic ★★ same type
ASAH1 p.Arg296Ter Pathogenic ★★ same type
ASAH1 p.Arg333Cys 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/asah1-p-glu99asp (accessed [today's date]).

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