Is BICRAL p.Phe598Ser (c.1793T>C) pathogenic?

BICRAL p.Phe598Ser (c.1793T>C) is classified Uncertain significance in BICRAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). AlphaMissense: likely benign (0.1237); Very rare (popmax 0.00339%, nfe).

How common is BICRAL p.Phe598Ser (c.1793T>C) in the general population?

BICRAL p.Phe598Ser (c.1793T>C) is very rare (popmax 0.00339%, nfe) (gnomAD).

What do computational predictors say about BICRAL p.Phe598Ser (c.1793T>C)?

AlphaMissense predicts likely benign (score 0.1237) — an in-silico prediction, not a clinical call.

BICRAL p.Phe598Ser

c.1793T>C · VCV3991478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1237 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1237	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -4.30	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 28 kb · p 7.8e-13 · regional, not allelic
Overall
CADD	22.9	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 0.00339% European (non-Finnish) · 40/1,179,924 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.0026% 42/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,498
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00133%	74,920

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.Phe598Ser
Coding: c.1793T>C
MANE Select: NM_001393499
Type: single nucleotide variant
Location: chr6:42830126 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.40
Residue 598: the 'disordered' region

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-phe598ser (accessed [today's date]).

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