Is SCAPER p.Ile1237Val (c.3709A>G) pathogenic?

SCAPER p.Ile1237Val (c.3709A>G) is classified Uncertain significance in SCAPER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-02). AlphaMissense: likely benign (0.0577); Very rare (popmax 0.00133%, afr).

How common is SCAPER p.Ile1237Val (c.3709A>G) in the general population?

SCAPER p.Ile1237Val (c.3709A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about SCAPER p.Ile1237Val (c.3709A>G)?

AlphaMissense predicts likely benign (score 0.0577) — an in-silico prediction, not a clinical call.

SCAPER p.Ile1237Val

c.3709A>G · VCV4925928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0577	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.23	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 -2.8
Regional constraint	o/e 0.90	unconstrained · MANE · 357 kb · p 0.0039 · regional, not allelic
Overall
CADD	9.892	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 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000186% 3/1,610,938 alleles · very rare exomes 3/1,458,754 · genomes 0/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
South Asian	0.0011%	90,600
European (non-Finnish)	8.49e-05%	1,178,355

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.Ile1237Val
Coding: c.3709A>G
MANE Select: NM_020843
Type: single nucleotide variant
Location: chr15:76376308 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.35 · 2 PDB
Residue 1237: an α-helix

Full SCAPER gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCAPER p.Arg112Ter Likely pathogenic ★★ same type
SCAPER p.Lys869Ter Pathogenic/Likely pathogenic ★★ same type
SCAPER p.Arg255Cys Uncertain significance ★★ ⚠ same type
SCAPER p.Arg500His Uncertain significance ★★ ⚠ same type
SCAPER p.Arg580Trp Uncertain significance ★★ ⚠ same type
SCAPER p.Asn460Asp Uncertain significance ★★ ⚠ same type
SCAPER p.Asp224Asn Uncertain significance ★★ ⚠ same type
SCAPER p.Gln1353His Uncertain significance ★★ ⚠ same type

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-ile1237val (accessed [today's date]).

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