Is CLPP p.Pro164fs (c.491del) pathogenic?

CLPP p.Pro164fs (c.491del) is classified Pathogenic in CLPP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). Absent from gnomAD v4.1.

How common is CLPP p.Pro164fs (c.491del) in the general population?

CLPP p.Pro164fs (c.491del) is absent from gnomAD v4.1 (gnomAD).

CLPP p.Pro164fs

c.491del · rs2145051196 · VCV1411562

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,936)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP -0.04, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,936). 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.Pro164fs
Coding: c.491del
MANE Select: NM_006012
dbSNP: rs2145051196
Type: Deletion
Location: chr19:6364572 (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.Ala10fs Pathogenic ★★ same type
CLPP p.Ser110fs Pathogenic ★ same type
CLPP p.Thr37fs Likely pathogenic ★ same type
CLPP c.555+106_555+107del Likely benign ★ same type
CLPP c.555+107del Benign ★ same type
CLPP c.556-14_556-4del Likely benign ★ same type
CLPP c.556-238_556-235del Likely benign ★ same type
CLPP c.556-295del Benign ★ 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-pro164fs (accessed [today's date]).

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