Is CABP4 p.Ser174= (c.522G>A) pathogenic?

CABP4 p.Ser174= (c.522G>A) is classified Conflicting classifications of pathogenicity in CABP4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.16%, amr); Associated with cone-rod synaptic disorder, congenital nonprogressive.

What condition is associated with CABP4 p.Ser174= (c.522G>A)?

CABP4 p.Ser174= (c.522G>A) is associated with cone-rod synaptic disorder, congenital nonprogressive (ClinVar).

How common is CABP4 p.Ser174= (c.522G>A) in the general population?

CABP4 p.Ser174= (c.522G>A) is rare (popmax 0.16%, amr) (gnomAD).

CABP4 p.Ser174=

c.522G>A · rs143344989 · VCV305652

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.16%, amr)

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 -20	GERP -5
Overall
CADD	0.051	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% Admixed American · 96/59,994 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0484% 780/1,611,752 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.16%	625
Remaining individualsnot grpmax-eligible	0.0592%	1,688
European (non-Finnish)	0.0531%	1,885
African / African-American	0.016%	6,242
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
Finnishnot grpmax-eligible	0.00647%	15,459
South Asian	0.00329%	30,360

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.Ser174=
Coding: c.522G>A
MANE Select: NM_145200
dbSNP: rs143344989
Type: single nucleotide variant
Location: chr11:67456423 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01

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-ser174 (accessed [today's date]).

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