Is RPAP1 p.Pro282Ser (c.844C>T) pathogenic?

RPAP1 p.Pro282Ser (c.844C>T) is classified Uncertain significance in RPAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.0795); Very rare (popmax 0.00119%, nfe).

How common is RPAP1 p.Pro282Ser (c.844C>T) in the general population?

RPAP1 p.Pro282Ser (c.844C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about RPAP1 p.Pro282Ser (c.844C>T)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

RPAP1 p.Pro282Ser

c.844C>T · VCV3435014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.9	GERP -2.8, phastCons 0.47
Regional constraint	o/e 0.90	unconstrained · MANE · 16 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	12.76	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 0.00119% European (non-Finnish) · 14/1,179,870 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,613,872 alleles · very rare exomes 14/1,461,704 · genomes 0/152,168 · joint denominator

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: RPAP1
Protein: p.Pro282Ser
Coding: c.844C>T
MANE Select: NM_015540
Type: single nucleotide variant
Location: chr15:41531122 (GRCh38)
Gene constraint: LOEUF 0.877 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.03
Residue 282: the 'disordered' region

Full RPAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPAP1 p.Ser3Leu Benign ★★ same type
RPAP1 p.Ala1022Val Uncertain significance ★ ⚠ same type
RPAP1 p.Ala1046Thr Uncertain significance ★ ⚠ same type
RPAP1 p.Ala1048Thr Uncertain significance ★ ⚠ same type
RPAP1 p.Ala1113Thr Uncertain significance ★ ⚠ same type
RPAP1 p.Ala1184Thr Uncertain significance ★ ⚠ same type
RPAP1 p.Ala1295Val Uncertain significance ★ ⚠ same type
RPAP1 p.Ala1310Val 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/rpap1-p-pro282ser (accessed [today's date]).

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