Is SCAPER p.Pro389Ser (c.1165C>T) pathogenic?

SCAPER p.Pro389Ser (c.1165C>T) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0649); No allele count reported in gnomAD v4.1 (AN 1,613,114); Associated with Inborn genetic diseases.

What condition is associated with SCAPER p.Pro389Ser (c.1165C>T)?

SCAPER p.Pro389Ser (c.1165C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SCAPER p.Pro389Ser (c.1165C>T) in the general population?

SCAPER p.Pro389Ser (c.1165C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,114) (gnomAD).

What do computational predictors say about SCAPER p.Pro389Ser (c.1165C>T)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

SCAPER p.Pro389Ser

c.1165C>T · rs2545811696 · VCV3158281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,114)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.70	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 1.4	GERP -0.62, phastCons 0.94
Regional constraint	o/e 0.94	unconstrained · MANE · 117 kb · p 0.18 · regional, not allelic
Overall
CADD	8.155	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

No allele count reported in gnomAD v4.1 (AN 1,613,114). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SCAPER
Protein: p.Pro389Ser
Coding: c.1165C>T
MANE Select: NM_020843
dbSNP: rs2545811696
Type: single nucleotide variant
Location: chr15:76771825 (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-pro389ser (accessed [today's date]).

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