Is PSAP p.Pro18Arg (c.53C>G) pathogenic?

PSAP p.Pro18Arg (c.53C>G) is classified Uncertain significance in PSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-28). AlphaMissense: likely benign (0.1913); Very rare (popmax 8.47e-05%, nfe).

How common is PSAP p.Pro18Arg (c.53C>G) in the general population?

PSAP p.Pro18Arg (c.53C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PSAP p.Pro18Arg (c.53C>G)?

AlphaMissense predicts likely benign (score 0.1913) — an in-silico prediction, not a clinical call.

PSAP p.Pro18Arg

c.53C>G · VCV4908002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1913	likely benign
REVEL	0.533	indeterminate
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	24.8	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,942 alleles

Overall 0.000124% 2/1,613,922 alleles · very rare exomes 2/1,461,588 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)grpmax	8.47e-05%	1,179,942

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PSAP
Protein: p.Pro18Arg
Coding: c.53C>G
MANE Select: NM_002778
Type: single nucleotide variant
Location: chr10:71834493 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 21 PDB
Residue 18: the saposin a-type 1 domain

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

Similar variants

PSAP p.Pro18Ala Uncertain significance ★ ⚠ same residue
PSAP p.Pro18Leu Uncertain significance ★ same residue
PSAP p.Pro18= Likely benign ★ same residue
PSAP c.1005+1G>A Pathogenic/Likely pathogenic ★★ same type
PSAP c.375+1G>T Likely pathogenic ★★ same type
PSAP c.576+1G>A Likely pathogenic ★★ same type
PSAP c.577-1G>T Pathogenic ★★ same type
PSAP c.721-1G>A 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/psap-p-pro18arg (accessed [today's date]).

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