Is CPAMD8 p.Ile239Val (c.715A>G) pathogenic?

CPAMD8 p.Ile239Val (c.715A>G) is classified Uncertain significance in CPAMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely benign (0.2545); Very rare (popmax 0.00034%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPAMD8 p.Ile239Val (c.715A>G)?

CPAMD8 p.Ile239Val (c.715A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CPAMD8 p.Ile239Val (c.715A>G) in the general population?

CPAMD8 p.Ile239Val (c.715A>G) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about CPAMD8 p.Ile239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.2545) — an in-silico prediction, not a clinical call.

CPAMD8 p.Ile239Val

c.715A>G · rs370553991 · VCV2239069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2545	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.09	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 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 24 kb · p 0.0018 · regional, not allelic
Overall
CADD	17.17	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 0.00034% European (non-Finnish) · 4/1,175,908 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000275% 4/1,454,792 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.Ile239Val
Coding: c.715A>G
MANE Select: NM_015692
dbSNP: rs370553991
Type: single nucleotide variant
Location: chr19:17002309 (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-ile239val (accessed [today's date]).

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