Is SCP2 p.Pro5Ala (c.13C>G) pathogenic?

SCP2 p.Pro5Ala (c.13C>G) is classified Uncertain significance in SCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-27). AlphaMissense: likely benign (0.0518); Absent from gnomAD v4.1.

How common is SCP2 p.Pro5Ala (c.13C>G) in the general population?

SCP2 p.Pro5Ala (c.13C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCP2 p.Pro5Ala (c.13C>G)?

AlphaMissense predicts likely benign (score 0.0518) — an in-silico prediction, not a clinical call.

SCP2 p.Pro5Ala

c.13C>G · rs1044388788 · VCV595570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0518 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0518	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -5.54	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 -7.7	GERP -2.4
Regional constraint	o/e 0.90	unconstrained · MANE · 112 kb · p 0.012 · regional, not allelic
Overall
CADD	0.035	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: SCP2
Protein: p.Pro5Ala
Coding: c.13C>G
MANE Select: NM_002979
dbSNP: rs1044388788
Type: single nucleotide variant
Location: chr1:52927409 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.39 · 2 PDB

Full SCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCP2 p.Pro5= Conflicting classifications of pathogenicity ★ same residue
SCP2 p.Pro5Leu Uncertain significance ★ ⚠ same residue
SCP2 p.Pro5Thr Uncertain significance ★ ⚠ same residue
SCP2 c.825+1G>T Pathogenic/Likely pathogenic ★★ same type
SCP2 p.Gln371Ter Pathogenic ★★ same type
SCP2 p.Ala359Val Uncertain significance ★★ ⚠ same type
SCP2 p.Ala427Gly Uncertain significance ★★ ⚠ same type
SCP2 p.Ala46Val 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/scp2-p-pro5ala (accessed [today's date]).

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