Is SCAPER p.Ser417Phe (c.1250C>T) pathogenic?

SCAPER p.Ser417Phe (c.1250C>T) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely pathogenic (0.9045); Absent from gnomAD v4.1; Associated with intellectual developmental disorder and retinitis pigmentosa; IDDRP.

What condition is associated with SCAPER p.Ser417Phe (c.1250C>T)?

SCAPER p.Ser417Phe (c.1250C>T) is associated with intellectual developmental disorder and retinitis pigmentosa; IDDRP (ClinVar).

How common is SCAPER p.Ser417Phe (c.1250C>T) in the general population?

SCAPER p.Ser417Phe (c.1250C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCAPER p.Ser417Phe (c.1250C>T)?

AlphaMissense predicts likely pathogenic (score 0.9045) — an in-silico prediction, not a clinical call.

SCAPER p.Ser417Phe

c.1250C>T · rs2063159864 · VCV2435663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9045 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

intellectual developmental disorder and retinitis pigmentosa; IDDRP

Computational evidence

Protein change
AlphaMissense	0.9045	likely pathogenic
REVEL	0.363	indeterminate
SaProt	LLR -7.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 117 kb · p 0.18 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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.Ser417Phe
Coding: c.1250C>T
MANE Select: NM_020843
dbSNP: rs2063159864
Type: single nucleotide variant
Location: chr15:76767087 (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

intellectual developmental disorder and retinitis pigmentosa; IDDRP — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCAPER p.Arg112Ter Likely pathogenic ★★ same condition
SCAPER p.Lys869Ter Pathogenic/Likely pathogenic ★★ same condition
SCAPER c.2645+36T>C Benign ★★ same condition
SCAPER c.3078+39G>T Benign ★★ same condition
SCAPER c.3705+3A>G Benign ★★ same condition
SCAPER c.612-4A>G Benign ★★ same condition
SCAPER c.772+1881G>T Benign ★★ same condition
SCAPER c.-42T>A Benign ★★ 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-ser417phe (accessed [today's date]).

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