Is BICRAL p.Ala42Val (c.125C>T) pathogenic?

BICRAL p.Ala42Val (c.125C>T) is classified Uncertain significance in BICRAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0874); Very rare (popmax 0.00267%, afr).

How common is BICRAL p.Ala42Val (c.125C>T) in the general population?

BICRAL p.Ala42Val (c.125C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BICRAL p.Ala42Val (c.125C>T)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

BICRAL p.Ala42Val

c.125C>T · VCV4208692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.72	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 6,623 bp · p 0.55 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.00267% African / African-American · 2/74,868 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,611,216 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BICRAL
Protein: p.Ala42Val
Coding: c.125C>T
MANE Select: NM_001393499
Type: single nucleotide variant
Location: chr6:42822969 (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.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
BICRAL p.Arg586Cys 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-ala42val (accessed [today's date]).

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