Is IQCB1 p.Pro563= (c.1689C>T) pathogenic?

IQCB1 p.Pro563= (c.1689C>T) is classified Likely benign in IQCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-11). Absent from gnomAD v4.1; Associated with nephronophthisis.

What condition is associated with IQCB1 p.Pro563= (c.1689C>T)?

IQCB1 p.Pro563= (c.1689C>T) is associated with nephronophthisis (ClinVar).

How common is IQCB1 p.Pro563= (c.1689C>T) in the general population?

IQCB1 p.Pro563= (c.1689C>T) is absent from gnomAD v4.1 (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

IQCB1 p.Pro563=

c.1689C>T · rs1947922675 · VCV1145271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

nephronophthisis

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 0.14	GERP -2.6, phastCons 0.66
Overall
CADD	6.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IQCB1
Protein: p.Pro563=
Coding: c.1689C>T
MANE Select: NM_001023570
dbSNP: rs1947922675
Type: single nucleotide variant
Location: chr3:121770453 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 563: the 'interaction with cep290, bbs1, bbs2, bbs4, bbs5, bbs7, bbs8 and bbs9' region; the 'interaction with bbs1, bbs2, bbs4, bbs7, bbs8 and bbs9' region

Full IQCB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

IQCB1 p.Pro563Ala Uncertain significance ★ ⚠ same residue
IQCB1 p.Pro563Arg Uncertain significance ★ same residue
IQCB1 c.264-2A>T Pathogenic ★★ same condition
IQCB1 c.488-1G>A Pathogenic/Likely pathogenic ★★ same condition
IQCB1 p.Arg332Ter Pathogenic ★★ same condition
IQCB1 p.Arg364Ter Pathogenic ★★ same condition
IQCB1 p.Arg445Ter Pathogenic ★★ same condition
IQCB1 p.Arg455Ter 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/iqcb1-p-pro563 (accessed [today's date]).

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