Is SCP2 p.Ala95Pro (c.283G>C) pathogenic?

SCP2 p.Ala95Pro (c.283G>C) is classified Uncertain significance in SCP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely pathogenic (0.9648); Absent from gnomAD v4.1.

How common is SCP2 p.Ala95Pro (c.283G>C) in the general population?

SCP2 p.Ala95Pro (c.283G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCP2 p.Ala95Pro (c.283G>C)?

AlphaMissense predicts likely pathogenic (score 0.9648) — an in-silico prediction, not a clinical call.

SCP2 p.Ala95Pro

c.283G>C · VCV3793302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9648	likely pathogenic · top 7% in SCP2
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -13.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62	GERP -3.8
Regional constraint	o/e 0.90	unconstrained · MANE · 112 kb · p 0.012 · regional, not allelic
Overall
CADD	18.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ala95Pro
Coding: c.283G>C
MANE Select: NM_002979
Type: single nucleotide variant
Location: chr1:52950838 (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.Ala95Ser Likely benign ★ 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
SCP2 p.Ala545Asp Uncertain significance ★★ same type
SCP2 p.Arg105Cys 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-ala95pro (accessed [today's date]).

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