Is CABP4 p.Pro22fs (c.65del) pathogenic?

CABP4 p.Pro22fs (c.65del) is classified Pathogenic/Likely pathogenic in CABP4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-27). Very rare (popmax 0.00443%, sas); Associated with CABP4-related disorder.

What condition is associated with CABP4 p.Pro22fs (c.65del)?

CABP4 p.Pro22fs (c.65del) is associated with CABP4-related disorder, cone-rod synaptic disorder, congenital nonprogressive (ClinVar).

How common is CABP4 p.Pro22fs (c.65del) in the general population?

CABP4 p.Pro22fs (c.65del) is very rare (popmax 0.00443%, sas) (gnomAD).

CABP4 p.Pro22fs

c.65del · rs775166854 · VCV866054

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00443%, sas)

Conditions

CABP4-related disorder

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 1.7	GERP -0.62, phastCons 0.96

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00443% South Asian · 4/90,362 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000896%

Overall 0.000435% 7/1,609,754 alleles · very rare exomes 7/1,457,410 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,686
South Asiangrpmax	0.00443%	22,590
Remaining individualsnot grpmax-eligible	0.0016%	62,338

Ashkenazi Jewish 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.Pro22fs
Coding: c.65del
MANE Select: NM_145200
dbSNP: rs775166854
Type: Deletion
Location: chr11:67455484 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 22: the 'disordered' region

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

Disease context

CABP4-related disorder

Also linked: cone-rod synaptic disorder, congenital nonprogressive

Similar variants

CABP4 p.Ala86fs Likely pathogenic ★★ same condition
CABP4 p.Arg124fs Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Pro22Ala Uncertain significance ★ ⚠ same residue
CABP4 p.Pro22Leu Uncertain significance ★ ⚠ same residue
CABP4 c.366+1G>T Pathogenic/Likely pathogenic ★★ same condition
CABP4 c.800_801delAG Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg216Ter Pathogenic ★★ 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/cabp4-p-pro22fs (accessed [today's date]).

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