Is SPINT2 p.Arg48= (c.144G>T) pathogenic?

SPINT2 p.Arg48= (c.144G>T) is classified Likely benign in SPINT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Ultra-rare (popmax 0.0111%, eas).

How common is SPINT2 p.Arg48= (c.144G>T) in the general population?

SPINT2 p.Arg48= (c.144G>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

SPINT2 p.Arg48=

c.144G>T · rs1421428605 · VCV2082743

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -1.5, phastCons 1
Overall
CADD	9.176	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,858 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000342% 5/1,461,890 alleles · ultra-rare

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: SPINT2
Protein: p.Arg48=
Coding: c.144G>T
MANE Select: NM_021102
dbSNP: rs1421428605
Type: single nucleotide variant
Location: chr19:38283664 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 1 PDB
Residue 48: a disulfide bond; the bpti/kunitz inhibitor 1 domain; a functional site (reactive bond)

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

Similar variants

SPINT2 p.Arg48Gln Uncertain significance ★ ⚠ same residue
SPINT2 p.Arg48Trp Uncertain significance ★ ⚠ same residue
SPINT2 p.Tyr163Cys Pathogenic ★★ same type
SPINT2 p.Ala2Val Uncertain significance ★★ ⚠ same type
SPINT2 p.Ala89Val Uncertain significance ★★ ⚠ same type
SPINT2 p.Arg182Cys Uncertain significance ★★ ⚠ same type
SPINT2 p.Arg182His Uncertain significance ★★ ⚠ same type
SPINT2 p.Arg185Cys 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/spint2-p-arg48 (accessed [today's date]).

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