Is SCAPER p.Ser840Pro (c.2518T>C) pathogenic?

SCAPER p.Ser840Pro (c.2518T>C) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely pathogenic (0.9789); Very rare (popmax 0.00131%, sas); Associated with Inborn genetic diseases.

What condition is associated with SCAPER p.Ser840Pro (c.2518T>C)?

SCAPER p.Ser840Pro (c.2518T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SCAPER p.Ser840Pro (c.2518T>C) in the general population?

SCAPER p.Ser840Pro (c.2518T>C) is very rare (popmax 0.00131%, sas) (gnomAD).

What do computational predictors say about SCAPER p.Ser840Pro (c.2518T>C)?

AlphaMissense predicts likely pathogenic (score 0.9789) — an in-silico prediction, not a clinical call.

SCAPER p.Ser840Pro

c.2518T>C · rs1361777325 · VCV2485056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00131%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9789	likely pathogenic
REVEL	0.427	indeterminate
SaProt	LLR -12.44	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 357 kb · p 0.0039 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00131% South Asian · 1/76,134 alleles

Overall 6.58e-05% 1/1,518,760 alleles · very rare exomes 1/1,366,570 · genomes 0/152,190 · 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.Ser840Pro
Coding: c.2518T>C
MANE Select: NM_020843
dbSNP: rs1361777325
Type: single nucleotide variant
Location: chr15:76665780 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.35 · 2 PDB

Full SCAPER 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

SCAPER p.Arg255Cys Uncertain significance ★★ ⚠ same condition
SCAPER p.Arg500His Uncertain significance ★★ ⚠ same condition
SCAPER p.Arg580Trp Uncertain significance ★★ ⚠ same condition
SCAPER p.Asn460Asp Uncertain significance ★★ ⚠ same condition
SCAPER p.Asp224Asn Uncertain significance ★★ ⚠ same condition
SCAPER p.Gln1353His Uncertain significance ★★ ⚠ same condition
SCAPER p.Gly264Glu Uncertain significance ★★ ⚠ same condition
SCAPER p.His1329Pro 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/scaper-p-ser840pro (accessed [today's date]).

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