Is PSAP p.Cys382Phe (c.1145G>T) pathogenic?

PSAP p.Cys382Phe (c.1145G>T) is classified Pathogenic in PSAP (ClinVar, No assertion criteria, 1 submitter; last evaluated 1991-06-17). AlphaMissense: likely pathogenic (0.955); Absent from gnomAD v4.1; Associated with Gaucher disease due to saposin C deficiency.

What condition is associated with PSAP p.Cys382Phe (c.1145G>T)?

PSAP p.Cys382Phe (c.1145G>T) is associated with Gaucher disease due to saposin C deficiency (ClinVar).

How common is PSAP p.Cys382Phe (c.1145G>T) in the general population?

PSAP p.Cys382Phe (c.1145G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSAP p.Cys382Phe (c.1145G>T)?

AlphaMissense predicts likely pathogenic (score 0.955) — an in-silico prediction, not a clinical call.

PSAP p.Cys382Phe

c.1145G>T · rs121918105 · VCV13364

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Gaucher disease due to saposin C deficiency

Computational evidence

Protein change
AlphaMissense	0.955	likely pathogenic ✓ concordant with ClinVar · top 6% in PSAP
REVEL	0.976	strongly pathogenic-leaning
SaProt	LLR -14.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	28.9	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: PSAP
Protein: p.Cys382Phe
Coding: c.1145G>T
MANE Select: NM_002778
dbSNP: rs121918105
Type: single nucleotide variant
Location: chr10:71819761 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 21 PDB
Residue 382: the saposin b-type 3 domain; a disulfide bond; an α-helix

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

Disease context

Gaucher disease due to saposin C deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSAP p.Cys382= Conflicting classifications of pathogenicity ★ same residue
PSAP p.Cys382Gly Pathogenic same residue
PSAP c.1005+1G>A Pathogenic/Likely pathogenic ★★ same condition
PSAP p.Asn215Lys Pathogenic/Likely pathogenic ★★ same condition
PSAP p.Gln50Ter Pathogenic ★★ same condition
PSAP p.Glu359Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
PSAP p.Met1Leu Pathogenic ★★ same condition
PSAP p.Thr217Ile Pathogenic/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/psap-p-cys382phe (accessed [today's date]).

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