Is CLPP p.Pro3= (c.9C>T) pathogenic?

CLPP p.Pro3= (c.9C>T) is classified Likely benign in CLPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). Very rare (popmax 0.0038%, nfe).

How common is CLPP p.Pro3= (c.9C>T) in the general population?

CLPP p.Pro3= (c.9C>T) is very rare (popmax 0.0038%, nfe) (gnomAD).

CLPP p.Pro3=

c.9C>T · VCV3611177

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0038%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.058	GERP -1.6
Overall
CADD	11.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0038% European (non-Finnish) · 41/1,078,952 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00254%

Overall 0.00305% 43/1,408,886 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0038%	26,316
Remaining individualsnot grpmax-eligible	0.00186%	53,668
Finnishnot grpmax-eligible	0.00181%	55,188

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: CLPP
Protein: p.Pro3=
Coding: c.9C>T
MANE Select: NM_006012
Type: single nucleotide variant
Location: chr19:6361583 (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

Similar variants

CLPP p.Pro3Ser Uncertain significance ★ same residue
CLPP c.368-2A>G Pathogenic/Likely pathogenic ★★ same type
CLPP p.Ala10Gly Uncertain significance ★★ ⚠ same type
CLPP p.Ala10Ser Uncertain significance ★★ ⚠ same type
CLPP p.Ala128Thr Uncertain significance ★★ ⚠ same type
CLPP p.Ala223Thr Uncertain significance ★★ ⚠ same type
CLPP p.Ala43Thr Uncertain significance ★★ ⚠ same type
CLPP p.Ala50Thr 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/clpp-p-pro3 (accessed [today's date]).

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