Is IQCB1 p.Ser44= (c.132A>G) pathogenic?

IQCB1 p.Ser44= (c.132A>G) is classified Likely benign in IQCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). Very rare (popmax 0.00447%, eas); Associated with nephronophthisis.

What condition is associated with IQCB1 p.Ser44= (c.132A>G)?

IQCB1 p.Ser44= (c.132A>G) is associated with nephronophthisis (ClinVar).

How common is IQCB1 p.Ser44= (c.132A>G) in the general population?

IQCB1 p.Ser44= (c.132A>G) is very rare (popmax 0.00447%, eas) (gnomAD).

How is Nephronophthisis inherited?

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

IQCB1 p.Ser44=

c.132A>G · VCV3665926

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

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 2.2	GERP 1.8, phastCons 1
Overall
CADD	10.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,748 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000125% 2/1,603,216 alleles · very rare exomes 2/1,450,912 · genomes 0/152,304 · joint denominator

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.Ser44=
Coding: c.132A>G
MANE Select: NM_001023570
Type: single nucleotide variant
Location: chr3:121828601 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05
Residue 44: the 'interaction with bbs1, 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 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
IQCB1 p.Arg461Ter Pathogenic ★★ same condition
IQCB1 p.Arg489Ter 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-ser44 (accessed [today's date]).

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