Is SCAPER p.Asp461Val (c.1382A>T) pathogenic?

SCAPER p.Asp461Val (c.1382A>T) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: ambiguous (0.5002); Ultra-rare (popmax 0.0107%, afr); Associated with intellectual developmental disorder and retinitis pigmentosa; IDDRP.

What condition is associated with SCAPER p.Asp461Val (c.1382A>T)?

SCAPER p.Asp461Val (c.1382A>T) is associated with intellectual developmental disorder and retinitis pigmentosa; IDDRP (ClinVar).

How common is SCAPER p.Asp461Val (c.1382A>T) in the general population?

SCAPER p.Asp461Val (c.1382A>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about SCAPER p.Asp461Val (c.1382A>T)?

AlphaMissense predicts ambiguous (score 0.5002) — an in-silico prediction, not a clinical call.

SCAPER p.Asp461Val

c.1382A>T · rs909818165 · VCV2435662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

intellectual developmental disorder and retinitis pigmentosa; IDDRP

Computational evidence

Protein change
AlphaMissense	0.5002	ambiguous
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 0.68, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 13 kb · p 0.074 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.0107% African / African-American · 8/74,720 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000622% 10/1,608,844 alleles · ultra-rare exomes 5/1,456,620 · genomes 5/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,340
European (non-Finnish)	0.00017%	589,095

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.Asp461Val
Coding: c.1382A>T
MANE Select: NM_020843
dbSNP: rs909818165
Type: single nucleotide variant
Location: chr15:76766955 (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-asp461val (accessed [today's date]).

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