Is CLPP p.Arg83Cys (c.247C>T) pathogenic?

CLPP p.Arg83Cys (c.247C>T) is classified Uncertain significance in CLPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely pathogenic (0.9898); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CLPP p.Arg83Cys (c.247C>T)?

CLPP p.Arg83Cys (c.247C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLPP p.Arg83Cys (c.247C>T) in the general population?

CLPP p.Arg83Cys (c.247C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLPP p.Arg83Cys (c.247C>T)?

AlphaMissense predicts likely pathogenic (score 0.9898) — an in-silico prediction, not a clinical call.

CLPP p.Arg83Cys

c.247C>T · VCV4003806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9898 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,154)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9898	likely pathogenic
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -14.50	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 7.5	GERP 0.79, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 6,803 bp · p 5e-05 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,598,154). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLPP
Protein: p.Arg83Cys
Coding: c.247C>T
MANE Select: NM_006012
Type: single nucleotide variant
Location: chr19:6361917 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.68 · 32 PDB

Full CLPP 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

CLPP p.Ala10Ser Uncertain significance ★★ ⚠ same condition
CLPP p.Ala128Thr Uncertain significance ★★ ⚠ same condition
CLPP p.Ala43Thr Uncertain significance ★★ ⚠ same condition
CLPP p.Ala50Thr Uncertain significance ★★ ⚠ same condition
CLPP p.Arg185Trp Uncertain significance ★★ ⚠ same condition
CLPP p.Gly8Ala Uncertain significance ★★ ⚠ same condition
CLPP p.Ile208Val Uncertain significance ★★ ⚠ same condition
CLPP p.Leu58Phe 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/clpp-p-arg83cys (accessed [today's date]).

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