Is SCAPER p.Ala280Val (c.839C>T) pathogenic?

SCAPER p.Ala280Val (c.839C>T) is classified Likely benign in SCAPER (ClinVar, Single submitter, 3 submitters; last evaluated 2024-11-23). AlphaMissense: likely benign (0.076); Rare (popmax 0.281%, mid); Associated with inherited retinal dystrophy.

What condition is associated with SCAPER p.Ala280Val (c.839C>T)?

SCAPER p.Ala280Val (c.839C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is SCAPER p.Ala280Val (c.839C>T) in the general population?

SCAPER p.Ala280Val (c.839C>T) is rare (popmax 0.281%, mid) (gnomAD).

What do computational predictors say about SCAPER p.Ala280Val (c.839C>T)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

SCAPER p.Ala280Val

c.839C>T · VCV3249448

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.281%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.40	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 5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 117 kb · p 0.18 · regional, not allelic
Overall
CADD	18.77	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 0.281% Middle Eastern · 17/6,058 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.0346% 558/1,613,716 alleles · rare exomes 476/1,461,474 · genomes 82/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.281%	356
Admixed American	0.107%	937
South Asian	0.0637%	1,570
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,850
Remaining individualsnot grpmax-eligible	0.0528%	1,893
European (non-Finnish)	0.031%	3,223
African / African-American	0.00533%	18,754

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.Ala280Val
Coding: c.839C>T
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76775051 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCAPER p.Arg1156= Likely benign ★★ same condition
SCAPER p.His1144Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
SCAPER p.Arg361Gln Likely benign ★ same condition
SCAPER c.1866+8A>G Conflicting classifications of pathogenicity same condition
SCAPER p.Arg404Ser Uncertain significance ⚠ same condition
SCAPER p.Glu1003Lys Uncertain significance ⚠ same condition
SCAPER p.Ile274Val Uncertain significance ⚠ same condition
SCAPER p.Ile370Val 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-ala280val (accessed [today's date]).

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