Is CPPED1 p.Leu295Val (c.883C>G) pathogenic?

CPPED1 p.Leu295Val (c.883C>G) is classified Uncertain significance in CPPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.1435); Very rare (popmax 8.48e-05%, nfe).

How common is CPPED1 p.Leu295Val (c.883C>G) in the general population?

CPPED1 p.Leu295Val (c.883C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CPPED1 p.Leu295Val (c.883C>G)?

AlphaMissense predicts likely benign (score 0.1435) — an in-silico prediction, not a clinical call.

CPPED1 p.Leu295Val

c.883C>G · VCV3496552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1435 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1435	likely benign
REVEL	0.556	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP -4.6, phastCons 0.001
Regional constraint	o/e 1.21	unconstrained · MANE · 139 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	13.74	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 8.48e-05% European (non-Finnish) · 1/1,179,080 alleles

Overall 6.85e-05% 1/1,459,108 alleles · very rare

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: CPPED1
Protein: p.Leu295Val
Coding: c.883C>G
MANE Select: NM_018340
Type: single nucleotide variant
Location: chr16:12664948 (GRCh38)
Gene constraint: LOEUF 1.288 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.46

Full CPPED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPPED1 p.Ala118Ser Uncertain significance ★ ⚠ same type
CPPED1 p.Ala192Val Uncertain significance ★ ⚠ same type
CPPED1 p.Ala200Thr Uncertain significance ★ ⚠ same type
CPPED1 p.Ala20Gly Uncertain significance ★ ⚠ same type
CPPED1 p.Ala20Pro Uncertain significance ★ ⚠ same type
CPPED1 p.Ala20Thr Uncertain significance ★ ⚠ same type
CPPED1 p.Ala238Thr Uncertain significance ★ ⚠ same type
CPPED1 p.Ala3Val 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/cpped1-p-leu295val (accessed [today's date]).

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