Is SCAPER p.Arg255Pro (c.764G>C) pathogenic?

SCAPER p.Arg255Pro (c.764G>C) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-18). AlphaMissense: likely benign (0.1566); Ultra-rare (popmax 0.0466%, sas).

How common is SCAPER p.Arg255Pro (c.764G>C) in the general population?

SCAPER p.Arg255Pro (c.764G>C) is ultra-rare (popmax 0.0466%, sas) (gnomAD).

What do computational predictors say about SCAPER p.Arg255Pro (c.764G>C)?

AlphaMissense predicts likely benign (score 0.1566) — an in-silico prediction, not a clinical call.

SCAPER p.Arg255Pro

c.764G>C · VCV4926010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1566 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0466%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1566	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -5.11	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 3.3	GERP 0.96, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 117 kb · p 0.18 · regional, not allelic
Overall
CADD	22.4	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 0.0466% South Asian · 42/90,050 alleles

Filtering AF 0.0354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0315%

Overall 0.00261% 42/1,607,364 alleles · ultra-rare exomes 40/1,455,178 · genomes 2/152,186 · 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: SCAPER
Protein: p.Arg255Pro
Coding: c.764G>C
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76795288 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.35 · 2 PDB
Residue 255: the 'disordered' region

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

Similar variants

SCAPER p.Arg255Cys Uncertain significance ★★ ⚠ same residue
SCAPER p.Arg255His Uncertain significance ★ ⚠ same residue
SCAPER p.Arg255Ser Uncertain significance ★ ⚠ same residue
SCAPER p.Arg112Ter Likely pathogenic ★★ same type
SCAPER p.Lys869Ter Pathogenic/Likely pathogenic ★★ same type
SCAPER p.Arg500His Uncertain significance ★★ ⚠ same type
SCAPER p.Arg580Trp Uncertain significance ★★ ⚠ same type
SCAPER p.Asn460Asp 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/scaper-p-arg255pro (accessed [today's date]).

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