Is CABP4 p.His105= (c.315C>T) pathogenic?

CABP4 p.His105= (c.315C>T) is classified Conflicting classifications of pathogenicity in CABP4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-01-29). Ultra-rare (popmax 0.0292%, sas); Associated with cone-rod synaptic disorder, congenital nonprogressive.

What condition is associated with CABP4 p.His105= (c.315C>T)?

CABP4 p.His105= (c.315C>T) is associated with cone-rod synaptic disorder, congenital nonprogressive (ClinVar).

How common is CABP4 p.His105= (c.315C>T) in the general population?

CABP4 p.His105= (c.315C>T) is ultra-rare (popmax 0.0292%, sas) (gnomAD).

CABP4 p.His105=

c.315C>T · rs756570102 · VCV305645

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0292%, sas)

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 -4.3
Overall
CADD	0.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0292% South Asian · 26/89,190 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0175%

Overall 0.00338% 49/1,449,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0292%	3,430
European (non-Finnish)	0.00187%	53,437
Remaining individualsnot grpmax-eligible	0.00161%	62,008

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.His105=
Coding: c.315C>T
MANE Select: NM_145200
dbSNP: rs756570102
Type: single nucleotide variant
Location: chr11:67455738 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 105: the 'disordered' region

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

GPR152 p.Arg105Cys Uncertain significance ★ ⚠ same residue
CABP4 p.His105Gln Likely benign ★ same residue
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

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-his105 (accessed [today's date]).

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