Is PSAP p.Leu22Pro (c.65T>C) pathogenic?

PSAP p.Leu22Pro (c.65T>C) is classified Uncertain significance in PSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0958); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PSAP p.Leu22Pro (c.65T>C)?

PSAP p.Leu22Pro (c.65T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PSAP p.Leu22Pro (c.65T>C) in the general population?

PSAP p.Leu22Pro (c.65T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSAP p.Leu22Pro (c.65T>C)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

PSAP p.Leu22Pro

c.65T>C · VCV4146061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.54	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 4.3	GERP 0.75, phastCons 1
Overall
CADD	20.9	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: PSAP
Protein: p.Leu22Pro
Coding: c.65T>C
MANE Select: NM_002778
Type: single nucleotide variant
Location: chr10:71834481 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 21 PDB
Residue 22: the saposin a-type 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSAP p.Ala13Val Uncertain significance ★★ ⚠ same condition
PSAP p.Ala30Val Uncertain significance ★★ ⚠ same condition
PSAP p.Arg213Gln Uncertain significance ★★ ⚠ same condition
PSAP p.Arg232His Uncertain significance ★★ ⚠ same condition
PSAP p.Arg392Trp Uncertain significance ★★ ⚠ same condition
PSAP p.Arg520His Uncertain significance ★★ ⚠ same condition
PSAP p.Asn422Lys Uncertain significance ★★ same condition
PSAP p.Asp111Ala Uncertain significance ★★ ⚠ 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-leu22pro (accessed [today's date]).

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