Is CPAMD8 p.Ser552fs (c.1654_1655del) pathogenic?

CPAMD8 p.Ser552fs (c.16541655del) is classified Likely pathogenic in CPAMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-06). Very rare (popmax 8.49e-05%, nfe); Associated with anterior segment dysgenesis 8.

What condition is associated with CPAMD8 p.Ser552fs (c.1654_1655del)?

CPAMD8 p.Ser552fs (c.1654_1655del) is associated with anterior segment dysgenesis 8 (ClinVar).

How common is CPAMD8 p.Ser552fs (c.1654_1655del) in the general population?

CPAMD8 p.Ser552fs (c.1654_1655del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

CPAMD8 p.Ser552fs

c.1654_1655del · VCV4880721

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

anterior segment dysgenesis 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 42
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP 0.91, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,462 alleles

Overall 6.21e-05% 1/1,611,544 alleles · very rare exomes 1/1,459,252 · genomes 0/152,292 · joint denominator

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.Ser552fs
Coding: c.1654_1655del
MANE Select: NM_015692
Type: Deletion
Location: chr19:16977471 (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

anterior segment dysgenesis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPAMD8 c.1758+1_1758+4del Pathogenic/Likely pathogenic ★★ same condition
CPAMD8 p.Asp714fs Likely pathogenic ★ same condition
CPAMD8 p.Gln1466fs Likely pathogenic ★ same condition
CPAMD8 c.2070+1G>A Pathogenic/Likely pathogenic ★★ same condition
CPAMD8 p.Arg1117Ter Likely pathogenic ★★ same condition
CPAMD8 p.Arg738fs Pathogenic ★★ same condition
CPAMD8 p.Trp178Ter Likely pathogenic ★★ same condition
CPAMD8 p.Asp169Gly 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-ser552fs (accessed [today's date]).

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