Is CLP1 p.Arg293Pro (c.878G>C) pathogenic?

CLP1 p.Arg293Pro (c.878G>C) is classified Uncertain significance in CLP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-15). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1.

How common is CLP1 p.Arg293Pro (c.878G>C) in the general population?

CLP1 p.Arg293Pro (c.878G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLP1 p.Arg293Pro (c.878G>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

CLP1 p.Arg293Pro

c.878G>C · rs1205528813 · VCV2826429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 5% in CLP1
REVEL	0.684	pathogenic-leaning
SaProt	LLR -16.45	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 1,956 bp · p 8.6e-16 · regional, not allelic
Overall
CADD	31.0	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: CLP1
Protein: p.Arg293Pro
Coding: c.878G>C
MANE Select: NM_006831
dbSNP: rs1205528813
Type: single nucleotide variant
Location: chr11:57661036 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 2 PDB
Residue 293: an α-helix

Full CLP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLP1 p.Arg293Trp Uncertain significance ★ ⚠ same residue
CLP1 p.Arg293= Likely benign ★ same residue
CLP1 p.Arg140His Pathogenic/Likely pathogenic ★★ same type
CLP1 p.Arg116Gln Uncertain significance ★★ ⚠ same type
CLP1 p.Arg143Cys Uncertain significance ★★ ⚠ same type
CLP1 p.Arg288Cys Uncertain significance ★★ ⚠ same type
CLP1 p.Arg288His Uncertain significance ★★ ⚠ same type
CLP1 p.Asn95Ser 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/clp1-p-arg293pro (accessed [today's date]).

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