Is CPAMD8 p.Pro309Arg (c.926C>G) pathogenic?

CPAMD8 p.Pro309Arg (c.926C>G) is classified Uncertain significance in CPAMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely benign (0.2982); Very rare (popmax 0.000777%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPAMD8 p.Pro309Arg (c.926C>G)?

CPAMD8 p.Pro309Arg (c.926C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CPAMD8 p.Pro309Arg (c.926C>G) in the general population?

CPAMD8 p.Pro309Arg (c.926C>G) is very rare (popmax 0.000777%, nfe) (gnomAD).

What do computational predictors say about CPAMD8 p.Pro309Arg (c.926C>G)?

AlphaMissense predicts likely benign (score 0.2982) — an in-silico prediction, not a clinical call.

CPAMD8 p.Pro309Arg

c.926C>G · rs762264386 · VCV2264958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000777%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2982	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -8.25	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 5.5	GERP 0.25, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 24 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	13.95	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 0.000777% European (non-Finnish) · 9/1,157,962 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000265%

Overall 0.000568% 9/1,583,314 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.Pro309Arg
Coding: c.926C>G
MANE Select: NM_015692
dbSNP: rs762264386
Type: single nucleotide variant
Location: chr19:16997280 (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-pro309arg (accessed [today's date]).

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