Is BICC1 p.Pro169Arg (c.506C>G) pathogenic?

BICC1 p.Pro169Arg (c.506C>G) is classified Uncertain significance in BICC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-06). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is BICC1 p.Pro169Arg (c.506C>G) in the general population?

BICC1 p.Pro169Arg (c.506C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICC1 p.Pro169Arg (c.506C>G)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

BICC1 p.Pro169Arg

c.506C>G · rs2132796942 · VCV1311699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 4% in BICC1
REVEL	0.771	pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 290 kb · p 0.054 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: BICC1
Protein: p.Pro169Arg
Coding: c.506C>G
MANE Select: NM_001080512
dbSNP: rs2132796942
Type: single nucleotide variant
Location: chr10:58787041 (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

Similar variants

BICC1 p.Pro169= Uncertain significance ★ same residue
BICC1 p.Ala190Thr Uncertain significance ★★ ⚠ same type
BICC1 p.Ala276Ser Uncertain significance ★★ ⚠ same type
BICC1 p.Ala523Val Uncertain significance ★★ ⚠ same type
BICC1 p.Arg302Gln Uncertain significance ★★ ⚠ same type
BICC1 p.Arg657Lys Uncertain significance ★★ ⚠ same type
BICC1 p.Arg804His Uncertain significance ★★ ⚠ same type
BICC1 p.Arg839His Uncertain significance ★★ ⚠ same type

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-pro169arg (accessed [today's date]).

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