Is BICRA p.Pro552Ser (c.1654C>T) pathogenic?

BICRA p.Pro552Ser (c.1654C>T) is classified Uncertain significance in BICRA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). AlphaMissense: likely benign (0.1686); Absent from gnomAD v4.1; Associated with BICRA-related disorder.

What condition is associated with BICRA p.Pro552Ser (c.1654C>T)?

BICRA p.Pro552Ser (c.1654C>T) is associated with BICRA-related disorder (ClinVar).

How common is BICRA p.Pro552Ser (c.1654C>T) in the general population?

BICRA p.Pro552Ser (c.1654C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICRA p.Pro552Ser (c.1654C>T)?

AlphaMissense predicts likely benign (score 0.1686) — an in-silico prediction, not a clinical call.

BICRA p.Pro552Ser

c.1654C>T · rs1973036340 · VCV2629980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1686 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BICRA-related disorder

Computational evidence

Protein change
AlphaMissense	0.1686	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -7.09	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 5.7	GERP 2.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 19 kb · p 1.1e-07 · regional, not allelic
Overall
CADD	22.8	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: BICRA
Protein: p.Pro552Ser
Coding: c.1654C>T
MANE Select: NM_001394372
dbSNP: rs1973036340
Type: single nucleotide variant
Location: chr19:47680824 (GRCh38)
Gene constraint: LOEUF 0.659 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 42.79

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

Disease context

BICRA-related disorder

Similar variants

BICRA p.Pro599Leu Uncertain significance ★★ ⚠ same condition
BICRA p.Val1322Met Likely pathogenic ★ ⚠ same condition
BICRA p.Glu1423Ter Uncertain significance ★ same condition
BICRA p.Gly88Arg Uncertain significance ★ ⚠ same condition
BICRA p.Leu366Val Uncertain significance ★ ⚠ same condition
BICRA p.Leu542Phe Uncertain significance ★ ⚠ same condition
BICRA p.Ile211Asn Uncertain significance ⚠ same condition
BICRA p.Pro394Gln 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/bicra-p-pro552ser (accessed [today's date]).

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