Is BICC1 p.Pro44Ala (c.130C>G) pathogenic?

BICC1 p.Pro44Ala (c.130C>G) is classified Uncertain significance in BICC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely benign (0.0814); Very rare (popmax 0.000254%, nfe); Associated with renal dysplasia, cystic, susceptibility to.

What condition is associated with BICC1 p.Pro44Ala (c.130C>G)?

BICC1 p.Pro44Ala (c.130C>G) is associated with renal dysplasia, cystic, susceptibility to (ClinVar).

How common is BICC1 p.Pro44Ala (c.130C>G) in the general population?

BICC1 p.Pro44Ala (c.130C>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BICC1 p.Pro44Ala (c.130C>G)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

BICC1 p.Pro44Ala

c.130C>G · VCV3595871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal dysplasia, cystic, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 290 kb · p 0.054 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,494 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,700 alleles · very rare

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.Pro44Ala
Coding: c.130C>G
MANE Select: NM_001080512
Type: single nucleotide variant
Location: chr10:58513273 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 61.02 · 3 PDB
Residue 44: the 'disordered' region

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.Pro44Leu Likely benign ★ 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-pro44ala (accessed [today's date]).

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