Is SPINT2 p.Arg9Trp (c.25C>T) pathogenic?

SPINT2 p.Arg9Trp (c.25C>T) is classified Uncertain significance in SPINT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1712); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SPINT2 p.Arg9Trp (c.25C>T)?

SPINT2 p.Arg9Trp (c.25C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SPINT2 p.Arg9Trp (c.25C>T) in the general population?

SPINT2 p.Arg9Trp (c.25C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPINT2 p.Arg9Trp (c.25C>T)?

AlphaMissense predicts likely benign (score 0.1712) — an in-silico prediction, not a clinical call.

SPINT2 p.Arg9Trp

c.25C>T · VCV4836101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1712 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,535,496)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1712	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP 0.52, phastCons 0.86
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 0.0014 · regional, not allelic
Overall
CADD	18.75	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

No allele count reported in gnomAD v4.1 (AN 1,535,496). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SPINT2
Protein: p.Arg9Trp
Coding: c.25C>T
MANE Select: NM_021102
Type: single nucleotide variant
Location: chr19:38264917 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 1 PDB

Full SPINT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPINT2 p.Arg9Pro Uncertain significance ★ ⚠ same residue
SPINT2 p.Ala2Val Uncertain significance ★★ ⚠ same condition
SPINT2 p.Ala89Val Uncertain significance ★★ ⚠ same condition
SPINT2 p.Arg182Cys Uncertain significance ★★ ⚠ same condition
SPINT2 p.Arg182His Uncertain significance ★★ ⚠ same condition
SPINT2 p.Arg225Gln Uncertain significance ★★ ⚠ same condition
SPINT2 p.Arg233Cys Uncertain significance ★★ ⚠ same condition
SPINT2 p.Asn136Ser 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/spint2-p-arg9trp (accessed [today's date]).

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