Is CABP4 p.Asp249= (c.747C>T) pathogenic?

CABP4 p.Asp249= (c.747C>T) is classified Benign in CABP4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Low-frequency (popmax 3.05%, afr); Associated with cone-rod synaptic disorder, congenital nonprogressive.

What condition is associated with CABP4 p.Asp249= (c.747C>T)?

CABP4 p.Asp249= (c.747C>T) is associated with cone-rod synaptic disorder, congenital nonprogressive (ClinVar).

How common is CABP4 p.Asp249= (c.747C>T) in the general population?

CABP4 p.Asp249= (c.747C>T) is low-frequency (popmax 3.05%, afr) (gnomAD).

CABP4 p.Asp249=

c.747C>T · rs34573687 · VCV707011

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.05%, afr)

Conditions

cone-rod synaptic disorder, congenital nonprogressive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.6
Overall
CADD	1.683	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.05% African / African-American · 2,284/74,898 alleles

Filtering AF 2.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.9%

Overall 0.176% 2,834/1,613,840 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.05%	33
Middle Eastern	0.379%	264
Remaining individualsnot grpmax-eligible	0.258%	388
Admixed American	0.237%	423
European (non-Finnish)	0.0186%	5,364
South Asian	0.00439%	22,766

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.Asp249=
Coding: c.747C>T
MANE Select: NM_145200
dbSNP: rs34573687
Type: single nucleotide variant
Location: chr11:67458466 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 249: the ef-hand 4 domain

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

Disease context

cone-rod synaptic disorder, congenital nonprogressive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CABP4 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg216Ter Pathogenic ★★ same condition
CABP4 p.Arg225Ter Pathogenic ★★ same condition
CABP4 p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg52Ter Pathogenic ★★ same condition
CABP4 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 c.*1117C>A Uncertain significance ★★ same condition
CABP4 c.*1158A>G 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/cabp4-p-asp249 (accessed [today's date]).

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