Is ASAH1 p.Pro89Ser (c.265C>T) pathogenic?

ASAH1 p.Pro89Ser (c.265C>T) is classified Uncertain significance in ASAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-06). AlphaMissense: likely benign (0.2385); Absent from gnomAD v4.1.

How common is ASAH1 p.Pro89Ser (c.265C>T) in the general population?

ASAH1 p.Pro89Ser (c.265C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASAH1 p.Pro89Ser (c.265C>T)?

AlphaMissense predicts likely benign (score 0.2385) — an in-silico prediction, not a clinical call.

ASAH1 p.Pro89Ser

c.265C>T · rs2117056336 · VCV1414136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2385 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2385	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -11.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.87, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 27 kb · p 6.4e-16 · regional, not allelic
Overall
CADD	24.8	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

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.Pro89Ser
Coding: c.265C>T
MANE Select: NM_177924
dbSNP: rs2117056336
Type: single nucleotide variant
Location: chr8:18069830 (GRCh38)
Gene constraint: LOEUF 1.435 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.97 · 2 PDB
Residue 89: a disulfide bond

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

Similar variants

ASAH1 p.Pro89Arg Uncertain significance ★★ ⚠ same residue
ASAH1 p.Pro89Ala Uncertain significance ★ ⚠ same residue
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

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-pro89ser (accessed [today's date]).

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