Is SPIN1 p.Arg37Trp (c.109C>T) pathogenic?

SPIN1 p.Arg37Trp (c.109C>T) is classified Uncertain significance in SPIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: ambiguous (0.5334); Absent from gnomAD v4.1.

How common is SPIN1 p.Arg37Trp (c.109C>T) in the general population?

SPIN1 p.Arg37Trp (c.109C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPIN1 p.Arg37Trp (c.109C>T)?

AlphaMissense predicts ambiguous (score 0.5334) — an in-silico prediction, not a clinical call.

SPIN1 p.Arg37Trp

c.109C>T · VCV4588925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5334 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5334	ambiguous
REVEL	0.138	moderately benign-leaning
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.25	acceptor loss, 7 bp away · masked 0 · deltas
Pangolin	Δ0.20	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 36 kb · p 0.00014 · regional, not allelic
Overall
CADD	26.5	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: SPIN1
Protein: p.Arg37Trp
Coding: c.109C>T
MANE Select: NM_006717
Type: single nucleotide variant
Location: chr9:88462503 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.14 · 20 PDB
Residue 37: the 'disordered' region

Full SPIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPIN1 p.Ala119Val Uncertain significance ★ ⚠ same type
SPIN1 p.Ala126Ser Uncertain significance ★ ⚠ same type
SPIN1 p.Arg117Gly Uncertain significance ★ ⚠ same type
SPIN1 p.Asn163Ser Uncertain significance ★ ⚠ same type
SPIN1 p.Asp198Tyr Uncertain significance ★ ⚠ same type
SPIN1 p.His127Arg Uncertain significance ★ ⚠ same type
SPIN1 p.Pro194Ser Uncertain significance ★ same type
SPIN1 p.Val82Leu 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/spin1-p-arg37trp (accessed [today's date]).

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