Is ASAH1 p.Cys31Phe (c.92G>T) pathogenic?

ASAH1 p.Cys31Phe (c.92G>T) is classified Likely pathogenic in ASAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-18). AlphaMissense: likely pathogenic (0.9328); Absent from gnomAD v4.1; Associated with Farber lipogranulomatosis.

What condition is associated with ASAH1 p.Cys31Phe (c.92G>T)?

ASAH1 p.Cys31Phe (c.92G>T) is associated with Farber lipogranulomatosis (ClinVar).

How common is ASAH1 p.Cys31Phe (c.92G>T) in the general population?

ASAH1 p.Cys31Phe (c.92G>T) is absent from gnomAD v4.1 (gnomAD).

How is Farber disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ASAH1 p.Cys31Phe (c.92G>T)?

AlphaMissense predicts likely pathogenic (score 0.9328) — an in-silico prediction, not a clinical call.

ASAH1 p.Cys31Phe

c.92G>T · rs1588999402 · VCV812489

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9328 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Farber lipogranulomatosis

Computational evidence

Protein change
AlphaMissense	0.9328	likely pathogenic ✓ concordant with ClinVar · top 10% in ASAH1
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -5.53	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 27 kb · p 6.4e-16 · regional, not allelic
Overall
CADD	28.6	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.Cys31Phe
Coding: c.92G>T
MANE Select: NM_177924
dbSNP: rs1588999402
Type: single nucleotide variant
Location: chr8:18075574 (GRCh38)
Gene constraint: LOEUF 1.435 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.97 · 2 PDB
Residue 31: a disulfide bond; an α-helix

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

Disease context

Farber lipogranulomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Farber disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Childhood, Infancy, Neonatal

Similar variants

ASAH1 p.Ile31Val Likely benign ★ same residue
ASAH1 c.1098+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASAH1 c.457+4A>G Pathogenic/Likely pathogenic ★★ same condition
ASAH1 c.648+1G>C Likely pathogenic ★★ same condition
ASAH1 p.Arg254Gly Pathogenic ★★ same condition
ASAH1 p.Arg333Cys Pathogenic/Likely pathogenic ★★ same condition
ASAH1 p.Arg333Gly Pathogenic/Likely pathogenic ★★ same condition
ASAH1 p.Asn320Ser 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/asah1-p-cys31phe (accessed [today's date]).

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