Is CPPED1 p.Asn76Ser (c.227A>G) pathogenic?

CPPED1 p.Asn76Ser (c.227A>G) is classified Uncertain significance in CPPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: likely benign (0.1291); Absent from gnomAD v4.1.

How common is CPPED1 p.Asn76Ser (c.227A>G) in the general population?

CPPED1 p.Asn76Ser (c.227A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPPED1 p.Asn76Ser (c.227A>G)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

CPPED1 p.Asn76Ser

c.227A>G · rs771169265 · VCV2559579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1291	likely benign
REVEL	0.704	pathogenic-leaning
SaProt	LLR -11.00	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 139 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPPED1
Protein: p.Asn76Ser
Coding: c.227A>G
MANE Select: NM_018340
dbSNP: rs771169265
Type: single nucleotide variant
Location: chr16:12781247 (GRCh38)
Gene constraint: LOEUF 1.288 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.46
Residue 76: the 'catalytic' region

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-asn76ser (accessed [today's date]).

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