Is CPAMD8 p.Ala64Pro (c.190G>C) pathogenic?

CPAMD8 p.Ala64Pro (c.190G>C) is classified Uncertain significance in CPAMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely pathogenic (0.8899); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CPAMD8 p.Ala64Pro (c.190G>C)?

CPAMD8 p.Ala64Pro (c.190G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CPAMD8 p.Ala64Pro (c.190G>C) in the general population?

CPAMD8 p.Ala64Pro (c.190G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPAMD8 p.Ala64Pro (c.190G>C)?

AlphaMissense predicts likely pathogenic (score 0.8899) — an in-silico prediction, not a clinical call.

CPAMD8 p.Ala64Pro

c.190G>C · VCV3496291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8899 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8899	likely pathogenic · top 8% in CPAMD8
REVEL	0.309	indeterminate
SaProt	LLR -14.40	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 24 kb · p 0.0018 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

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

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: CPAMD8
Protein: p.Ala64Pro
Coding: c.190G>C
MANE Select: NM_015692
Type: single nucleotide variant
Location: chr19:17022084 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.99

Full CPAMD8 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

CPAMD8 c.-54C>G Uncertain significance ★★ same condition
CPAMD8 p.Ala1236Thr Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Ala1468Glu Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Ala490Thr Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg1186His Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg171Gln Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg402His Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg631Pro 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/cpamd8-p-ala64pro (accessed [today's date]).

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