Is CABP4 p.Ala23fs (c.66dup) pathogenic?

CABP4 p.Ala23fs (c.66dup) is classified Pathogenic in CABP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-10). Very rare (popmax 8.49e-05%, nfe).

How common is CABP4 p.Ala23fs (c.66dup) in the general population?

CABP4 p.Ala23fs (c.66dup) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

CABP4 p.Ala23fs

c.66dup · rs1864734117 · VCV1383967

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

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 1 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.7, phastCons 0.007

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) · 1/1,178,522 alleles

Overall 0.000137% 2/1,456,526 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,296
European (non-Finnish)grpmax	8.49e-05%	1,178,523

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CABP4
Protein: p.Ala23fs
Coding: c.66dup
MANE Select: NM_145200
dbSNP: rs1864734117
Type: Duplication
Location: chr11:67455488 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 23: the 'disordered' region

Full CABP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABP4 p.Ala23Val Likely benign ★★ same residue
CABP4 p.Ala23= Conflicting classifications of pathogenicity ★ same residue
CABP4 p.Ala23Gly Uncertain significance ★ ⚠ same residue
CABP4 p.Glu153fs Pathogenic ★★ same type
CABP4 p.Gln9fs Pathogenic ★ same type
CABP4 p.Gly121fs Likely pathogenic ★ same type
CABP4 p.Leu198fs Pathogenic ★ same type
CABP4 p.Pro114fs Pathogenic ★ same type

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/cabp4-p-ala23fs (accessed [today's date]).

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