Is PRAP1 p.Pro53Arg (c.158C>G) pathogenic?

PRAP1 p.Pro53Arg (c.158C>G) is classified Uncertain significance in PRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.1476); Very rare (popmax 0.00133%, afr).

How common is PRAP1 p.Pro53Arg (c.158C>G) in the general population?

PRAP1 p.Pro53Arg (c.158C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PRAP1 p.Pro53Arg (c.158C>G)?

AlphaMissense predicts likely benign (score 0.1476) — an in-silico prediction, not a clinical call.

PRAP1 p.Pro53Arg

c.158C>G · VCV3309697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1476 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1476	likely benign
REVEL	0.044	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 -3.9	GERP -2
Regional constraint	o/e 0.83	unconstrained · MANE · 5,019 bp · p 0.015 · regional, not allelic
Overall
CADD	7.379	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 0.00133% African / African-American · 1/74,980 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,612,880 alleles · very rare exomes 4/1,460,688 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,980
European (non-Finnish)	0.000254%	393,321

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: PRAP1
Protein: p.Pro53Arg
Coding: c.158C>G
MANE Select: NM_145202
Type: single nucleotide variant
Location: chr10:133352036 (GRCh38)
Gene constraint: LOEUF 1.401 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.73

Full PRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRAP1 p.Ala47Thr Uncertain significance ★ ⚠ same type
PRAP1 p.Arg125Lys Uncertain significance ★ ⚠ same type
PRAP1 p.Arg48His Uncertain significance ★ ⚠ same type
PRAP1 p.Arg78Gln Uncertain significance ★ ⚠ same type
PRAP1 p.Asp108Asn Uncertain significance ★ ⚠ same type
PRAP1 p.Asp108His Uncertain significance ★ ⚠ same type
PRAP1 p.Asp97Glu Uncertain significance ★ ⚠ same type
PRAP1 p.Glu123Lys Uncertain significance ★ ⚠ 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/prap1-p-pro53arg (accessed [today's date]).

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