Is SCAPER p.Pro900Ala (c.2698C>G) pathogenic?

SCAPER p.Pro900Ala (c.2698C>G) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.144); Very rare (popmax 0.00447%, eas); Associated with Inborn genetic diseases.

What condition is associated with SCAPER p.Pro900Ala (c.2698C>G)?

SCAPER p.Pro900Ala (c.2698C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SCAPER p.Pro900Ala (c.2698C>G) in the general population?

SCAPER p.Pro900Ala (c.2698C>G) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about SCAPER p.Pro900Ala (c.2698C>G)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

SCAPER p.Pro900Ala

c.2698C>G · VCV3792970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.144	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -9.26	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 357 kb · p 0.0039 · regional, not allelic
Overall
CADD	23.4	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 0.00447% East Asian · 2/44,778 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000187% 3/1,607,294 alleles · very rare exomes 3/1,455,010 · genomes 0/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,389
South Asian	0.00112%	89,438

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.Pro900Ala
Coding: c.2698C>G
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76621777 (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-pro900ala (accessed [today's date]).

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