Is CPPED1 p.Ala192Val (c.575C>T) pathogenic?

CPPED1 p.Ala192Val (c.575C>T) is classified Uncertain significance in CPPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-03). AlphaMissense: likely benign (0.145); Ultra-rare (popmax 0.0132%, sas).

How common is CPPED1 p.Ala192Val (c.575C>T) in the general population?

CPPED1 p.Ala192Val (c.575C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about CPPED1 p.Ala192Val (c.575C>T)?

AlphaMissense predicts likely benign (score 0.145) — an in-silico prediction, not a clinical call.

CPPED1 p.Ala192Val

c.575C>T · VCV4233490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.145 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.145	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -6.94	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 8.7	GERP 3.8, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 139 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	18.31	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 0.0132% South Asian · 12/91,082 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00173% 28/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,590
African / African-American	0.0107%	9,380
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.000424%	236,007

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.Ala192Val
Coding: c.575C>T
MANE Select: NM_018340
Type: single nucleotide variant
Location: chr16:12704764 (GRCh38)
Gene constraint: LOEUF 1.288 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.46
Residue 192: 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.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
CPPED1 p.Ala94Thr 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-ala192val (accessed [today's date]).

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