Is PRSS12 p.Pro700Ser (c.2098C>T) pathogenic?

PRSS12 p.Pro700Ser (c.2098C>T) is classified Uncertain significance in PRSS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.2155); Absent from gnomAD v4.1.

How common is PRSS12 p.Pro700Ser (c.2098C>T) in the general population?

PRSS12 p.Pro700Ser (c.2098C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRSS12 p.Pro700Ser (c.2098C>T)?

AlphaMissense predicts likely benign (score 0.2155) — an in-silico prediction, not a clinical call.

PRSS12 p.Pro700Ser

c.2098C>T · rs2530532126 · VCV3219800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2155 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2155	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 71 kb · p 0.96 · regional, not allelic
Overall
CADD	27.0	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

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: PRSS12
Protein: p.Pro700Ser
Coding: c.2098C>T
MANE Select: NM_003619
dbSNP: rs2530532126
Type: single nucleotide variant
Location: chr4:118283053 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 700: a disulfide bond; the peptidase s1 domain

Full PRSS12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRSS12 c.2320+6G>C Uncertain significance ★★ same type
PRSS12 c.821-1G>A Uncertain significance ★★ same type
PRSS12 c.*1615C>T Uncertain significance ★★ same type
PRSS12 c.*221A>T Uncertain significance ★★ same type
PRSS12 p.Ala547Asp Uncertain significance ★★ ⚠ same type
PRSS12 p.Ala79Pro Uncertain significance ★★ ⚠ same type
PRSS12 p.Arg292Trp Uncertain significance ★★ ⚠ same type
PRSS12 p.Arg426Gln 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/prss12-p-pro700ser (accessed [today's date]).

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