Is CLPP p.Ala267Val (c.800C>T) pathogenic?

CLPP p.Ala267Val (c.800C>T) is classified Uncertain significance in CLPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0172%, mid); Associated with Inborn genetic diseases.

What condition is associated with CLPP p.Ala267Val (c.800C>T)?

CLPP p.Ala267Val (c.800C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLPP p.Ala267Val (c.800C>T) in the general population?

CLPP p.Ala267Val (c.800C>T) is ultra-rare (popmax 0.0172%, mid) (gnomAD).

What do computational predictors say about CLPP p.Ala267Val (c.800C>T)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

CLPP p.Ala267Val

c.800C>T · rs759816700 · VCV2390946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -0.85, phastCons 0.011
Regional constraint	o/e 0.76	unconstrained · MANE · 6,803 bp · p 5e-05 · regional, not allelic
Overall
CADD	9.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0172% Middle Eastern · 1/5,810 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00543%

Overall 0.00561% 88/1,569,506 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0172%	5,810
European (non-Finnish)	0.00717%	13,945
Remaining individualsnot grpmax-eligible	0.00658%	15,208

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.Ala267Val
Coding: c.800C>T
MANE Select: NM_006012
dbSNP: rs759816700
Type: single nucleotide variant
Location: chr19:6368676 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.68 · 32 PDB
Residue 267: the 'disordered' region

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.Ala267= Benign ★★ same residue
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

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-ala267val (accessed [today's date]).

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