Is BICRAL p.Pro648Ser (c.1942C>T) pathogenic?

BICRAL p.Pro648Ser (c.1942C>T) is classified Uncertain significance in BICRAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.086); Absent from gnomAD v4.1.

How common is BICRAL p.Pro648Ser (c.1942C>T) in the general population?

BICRAL p.Pro648Ser (c.1942C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICRAL p.Pro648Ser (c.1942C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

BICRAL p.Pro648Ser

c.1942C>T · VCV3991479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,594,166)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.56	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 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 28 kb · p 7.8e-13 · regional, not allelic
Overall
CADD	21.1	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

No allele count reported in gnomAD v4.1 (AN 1,594,166). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BICRAL
Protein: p.Pro648Ser
Coding: c.1942C>T
MANE Select: NM_001393499
Type: single nucleotide variant
Location: chr6:42852194 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.40

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

Similar variants

BICRAL p.Ala42Val Uncertain significance ★ ⚠ same type
BICRAL p.Ala479Gly Uncertain significance ★ ⚠ same type
BICRAL p.Ala546Gly Uncertain significance ★ ⚠ same type
BICRAL p.Ala695Val Uncertain significance ★ ⚠ same type
BICRAL p.Ala729Val Uncertain significance ★ ⚠ same type
BICRAL p.Ala833Asp Uncertain significance ★ ⚠ same type
BICRAL p.Ala889Thr Uncertain significance ★ ⚠ same type
BICRAL p.Arg1022Gln 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/bicral-p-pro648ser (accessed [today's date]).

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