Is BICC1 p.Pro520Ser (c.1558C>T) pathogenic?

BICC1 p.Pro520Ser (c.1558C>T) is classified Uncertain significance in BICC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-03). AlphaMissense: likely benign (0.1865); Absent from gnomAD v4.1.

How common is BICC1 p.Pro520Ser (c.1558C>T) in the general population?

BICC1 p.Pro520Ser (c.1558C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICC1 p.Pro520Ser (c.1558C>T)?

AlphaMissense predicts likely benign (score 0.1865) — an in-silico prediction, not a clinical call.

BICC1 p.Pro520Ser

c.1558C>T · VCV4716781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1865	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -6.90	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 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 290 kb · p 0.054 · regional, not allelic
Overall
CADD	22.4	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

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.Pro520Ser
Coding: c.1558C>T
MANE Select: NM_001080512
Type: single nucleotide variant
Location: chr10:58799085 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 61.02 · 3 PDB

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

Similar variants

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
BICC1 p.Arg961Cys 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-pro520ser (accessed [today's date]).

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