Is SPINT2 p.Asn57Ser (c.170A>G) pathogenic?

SPINT2 p.Asn57Ser (c.170A>G) is classified Uncertain significance in SPINT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). AlphaMissense: likely benign (0.1437); Ultra-rare (popmax 0.0164%, mid).

How common is SPINT2 p.Asn57Ser (c.170A>G) in the general population?

SPINT2 p.Asn57Ser (c.170A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about SPINT2 p.Asn57Ser (c.170A>G)?

AlphaMissense predicts likely benign (score 0.1437) — an in-silico prediction, not a clinical call.

SPINT2 p.Asn57Ser

c.170A>G · rs143771318 · VCV1438600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1437 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1437	likely benign
REVEL	0.665	pathogenic-leaning
SaProt	LLR -8.42	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 0.0014 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00204% 33/1,614,002 alleles · ultra-rare exomes 32/1,461,890 · genomes 1/152,112 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00254%	39,335
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00134%	74,892

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.Asn57Ser
Coding: c.170A>G
MANE Select: NM_021102
dbSNP: rs143771318
Type: single nucleotide variant
Location: chr19:38283690 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 1 PDB
Residue 57: a β-strand; the bpti/kunitz inhibitor 1 domain

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

Similar variants

SPINT2 p.Asn57= Likely benign ★ same residue
SPINT2 p.Asn57fs Pathogenic ★★ 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-asn57ser (accessed [today's date]).

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