Is BICC1 p.Pro169= (c.507A>G) pathogenic?

BICC1 p.Pro169= (c.507A>G) is classified Uncertain significance in BICC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Very rare (popmax 0.00271%, afr); Associated with renal dysplasia, cystic, susceptibility to.

What condition is associated with BICC1 p.Pro169= (c.507A>G)?

BICC1 p.Pro169= (c.507A>G) is associated with renal dysplasia, cystic, susceptibility to (ClinVar).

How common is BICC1 p.Pro169= (c.507A>G) in the general population?

BICC1 p.Pro169= (c.507A>G) is very rare (popmax 0.00271%, afr) (gnomAD).

BICC1 p.Pro169=

c.507A>G · VCV3595925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Conditions

renal dysplasia, cystic, susceptibility to

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 1.1	GERP -5.1, phastCons 0.99
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% African / African-American · 2/73,702 alleles

Filtering AF 0.00045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000169%

Overall 0.000625% 10/1,599,676 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00485%	20,622
African / African-Americangrpmax	0.00271%	36,851
Admixed American	0.00174%	57,448
European (non-Finnish)	0.000341%	293,672

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BICC1
Protein: p.Pro169=
Coding: c.507A>G
MANE Select: NM_001080512
Type: single nucleotide variant
Location: chr10:58787042 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 61.02 · 3 PDB
Residue 169: the kh 1 domain

Full BICC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal dysplasia, cystic, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BICC1 p.Pro169Arg Uncertain significance ★ ⚠ same residue
BICC1 p.Ala276Ser Uncertain significance ★★ ⚠ same condition
BICC1 p.Arg804His Uncertain significance ★★ ⚠ same condition
BICC1 p.Arg839His Uncertain significance ★★ ⚠ same condition
BICC1 p.Asn236Ser Uncertain significance ★★ ⚠ same condition
BICC1 p.Asn259Asp Uncertain significance ★★ ⚠ same condition
BICC1 p.Asn476Ser Uncertain significance ★★ ⚠ same condition
BICC1 p.Asp578Ala 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/bicc1-p-pro169 (accessed [today's date]).

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