Is IQCB1 p.Arg445= (c.1335A>T) pathogenic?

IQCB1 p.Arg445= (c.1335A>T) is classified Likely benign in IQCB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-16). Ultra-rare (popmax 0.0165%, mid); Associated with nephronophthisis.

What condition is associated with IQCB1 p.Arg445= (c.1335A>T)?

IQCB1 p.Arg445= (c.1335A>T) is associated with nephronophthisis (ClinVar).

How common is IQCB1 p.Arg445= (c.1335A>T) in the general population?

IQCB1 p.Arg445= (c.1335A>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Nephronophthisis inherited?

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

IQCB1 p.Arg445=

c.1335A>T · rs772003773 · VCV698880

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 0.64	GERP 0.65, phastCons 0.67
Overall
CADD	5.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0106% 171/1,613,878 alleles · ultra-rare exomes 160/1,461,568 · genomes 11/152,310 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.0138%	7,238
Remaining individualsnot grpmax-eligible	0.0048%	20,830
African / African-American	0.004%	25,011
Finnishnot grpmax-eligible	0.00156%	64,014

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: IQCB1
Protein: p.Arg445=
Coding: c.1335A>T
MANE Select: NM_001023570
dbSNP: rs772003773
Type: single nucleotide variant
Location: chr3:121781818 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 445: the 'interaction with cep290, bbs1, bbs2, bbs4, bbs5, 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.Arg445Ter Pathogenic ★★ same residue
IQCB1 p.Arg445Gln 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.Arg455Ter Pathogenic ★★ same condition
IQCB1 p.Arg461Ter 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-arg445 (accessed [today's date]).

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