Is SCAPER p.Met486Val (c.1456A>G) pathogenic?

SCAPER p.Met486Val (c.1456A>G) is classified Uncertain significance in SCAPER (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.0743); Very rare (popmax 0.00227%, eas); Associated with inherited retinal dystrophy.

What condition is associated with SCAPER p.Met486Val (c.1456A>G)?

SCAPER p.Met486Val (c.1456A>G) is associated with inherited retinal dystrophy (ClinVar).

How common is SCAPER p.Met486Val (c.1456A>G) in the general population?

SCAPER p.Met486Val (c.1456A>G) is very rare (popmax 0.00227%, eas) (gnomAD).

What do computational predictors say about SCAPER p.Met486Val (c.1456A>G)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

SCAPER p.Met486Val

c.1456A>G · VCV3249290

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00227%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.89	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 1.6	GERP -3.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 13 kb · p 0.074 · regional, not allelic
Overall
CADD	12.5	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

Grpmax group 0.00227% East Asian · 1/43,998 alleles

Overall 6.3e-05% 1/1,588,558 alleles · very rare exomes 0/1,436,322 · genomes 1/152,236 · joint denominator

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.Met486Val
Coding: c.1456A>G
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76765602 (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.Met486Ile Uncertain significance ★ ⚠ same residue
SCAPER p.Arg1156= Likely benign ★★ same condition
SCAPER p.His1144Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
SCAPER p.Ala280Val Likely benign ★ 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

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-met486val (accessed [today's date]).

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