Is CPAMD8 p.Pro1504Arg (c.4511C>G) pathogenic?

CPAMD8 p.Pro1504Arg (c.4511C>G) is classified Uncertain significance in CPAMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: ambiguous (0.3619); Very rare (popmax 0.000521%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPAMD8 p.Pro1504Arg (c.4511C>G)?

CPAMD8 p.Pro1504Arg (c.4511C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CPAMD8 p.Pro1504Arg (c.4511C>G) in the general population?

CPAMD8 p.Pro1504Arg (c.4511C>G) is very rare (popmax 0.000521%, nfe) (gnomAD).

What do computational predictors say about CPAMD8 p.Pro1504Arg (c.4511C>G)?

AlphaMissense predicts ambiguous (score 0.3619) — an in-silico prediction, not a clinical call.

CPAMD8 p.Pro1504Arg

c.4511C>G · VCV4006118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000521%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3619	ambiguous
REVEL	0.314	indeterminate
SaProt	LLR -7.46	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -1.1, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 83 kb · p 0.29 · regional, not allelic
Overall
CADD	18.99	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 0.000521% European (non-Finnish) · 6/1,151,498 alleles

Filtering AF 0.000187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000123%

Overall 0.000425% 6/1,410,860 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: CPAMD8
Protein: p.Pro1504Arg
Coding: c.4511C>G
MANE Select: NM_015692
Type: single nucleotide variant
Location: chr19:16902823 (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-pro1504arg (accessed [today's date]).

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