Is PRSS56 p.Ser48Arg (c.144C>G) pathogenic?

PRSS56 p.Ser48Arg (c.144C>G) is classified Uncertain significance in PRSS56 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.2979); Very rare (popmax 0.00137%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRSS56 p.Ser48Arg (c.144C>G)?

PRSS56 p.Ser48Arg (c.144C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRSS56 p.Ser48Arg (c.144C>G) in the general population?

PRSS56 p.Ser48Arg (c.144C>G) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about PRSS56 p.Ser48Arg (c.144C>G)?

AlphaMissense predicts likely benign (score 0.2979) — an in-silico prediction, not a clinical call.

PRSS56 p.Ser48Arg

c.144C>G · VCV4145892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2979	likely benign
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor loss, 46 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -10	GERP -2.9
Regional constraint	o/e 1.00	unconstrained · MANE · 2,232 bp · p 0.94 · regional, not allelic
Overall
CADD	5.815	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; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,064 alleles

Overall 6.51e-05% 1/1,536,018 alleles · very rare exomes 0/1,383,788 · genomes 1/152,230 · joint denominator

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: PRSS56
Protein: p.Ser48Arg
Coding: c.144C>G
MANE Select: NM_001195129
Type: single nucleotide variant
Location: chr2:232521367 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.35

Full PRSS56 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

PRSS56 p.Ser48= Likely benign ★★ same residue
PRSS56 p.Ala502Thr Uncertain significance ★★ ⚠ same condition
PRSS56 p.Asp254Asn Uncertain significance ★★ ⚠ same condition
PRSS56 p.Asp285Asn Uncertain significance ★★ ⚠ same condition
PRSS56 p.Gly538Ser Uncertain significance ★★ ⚠ same condition
PRSS56 p.Leu483Phe Uncertain significance ★★ ⚠ same condition
PRSS56 p.Pro354Ala Uncertain significance ★★ ⚠ same condition
PRSS56 p.Pro544Leu 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/prss56-p-ser48arg (accessed [today's date]).

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