Is SCAPER p.His230Pro (c.689A>C) pathogenic?

SCAPER p.His230Pro (c.689A>C) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0923); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SCAPER p.His230Pro (c.689A>C)?

SCAPER p.His230Pro (c.689A>C) is associated with Inborn genetic diseases (ClinVar).

How common is SCAPER p.His230Pro (c.689A>C) in the general population?

SCAPER p.His230Pro (c.689A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCAPER p.His230Pro (c.689A>C)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

SCAPER p.His230Pro

c.689A>C · VCV4160237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -5.28	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 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 117 kb · p 0.18 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCAPER
Protein: p.His230Pro
Coding: c.689A>C
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76795363 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.35 · 2 PDB
Residue 230: the 'disordered' region

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.His230Arg Uncertain significance ★★ ⚠ same residue
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

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-his230pro (accessed [today's date]).

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