Is CPPED1 p.Ala23Ser (c.67G>T) pathogenic?

CPPED1 p.Ala23Ser (c.67G>T) is classified Likely benign in CPPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.0918); Ultra-rare (popmax 0.0171%, eas).

How common is CPPED1 p.Ala23Ser (c.67G>T) in the general population?

CPPED1 p.Ala23Ser (c.67G>T) is ultra-rare (popmax 0.0171%, eas) (gnomAD).

What do computational predictors say about CPPED1 p.Ala23Ser (c.67G>T)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

CPPED1 p.Ala23Ser

c.67G>T · rs766353865 · VCV2589534

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.84	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 1.2	GERP 0.74, phastCons 0.98
Regional constraint	o/e 1.21	unconstrained · MANE · 139 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	13.19	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

Grpmax group 0.0171% East Asian · 7/40,920 alleles

Filtering AF 0.00798% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.000507% 8/1,576,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0171%	5,846
Remaining individualsnot grpmax-eligible	0.00164%	60,948

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.Ala23Ser
Coding: c.67G>T
MANE Select: NM_018340
dbSNP: rs766353865
Type: single nucleotide variant
Location: chr16:12803710 (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-ala23ser (accessed [today's date]).

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