Is BICRAL p.Val192Ala (c.575T>C) pathogenic?

BICRAL p.Val192Ala (c.575T>C) is classified Uncertain significance in BICRAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely pathogenic (0.6454); Absent from gnomAD v4.1.

How common is BICRAL p.Val192Ala (c.575T>C) in the general population?

BICRAL p.Val192Ala (c.575T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BICRAL p.Val192Ala (c.575T>C)?

AlphaMissense predicts likely pathogenic (score 0.6454) — an in-silico prediction, not a clinical call.

BICRAL p.Val192Ala

c.575T>C · VCV3824331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6454 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6454	likely pathogenic
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 28 kb · p 7.8e-13 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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: BICRAL
Protein: p.Val192Ala
Coding: c.575T>C
MANE Select: NM_001393499
Type: single nucleotide variant
Location: chr6:42828908 (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-val192ala (accessed [today's date]).

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