Is CABYR c.541+445A>C pathogenic?

CABYR c.541+445A>C is classified Uncertain significance in CABYR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.1331); Absent from gnomAD v4.1.

How common is CABYR c.541+445A>C in the general population?

CABYR c.541+445A>C is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CABYR c.541+445A>C?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

CABYR c.541+445A>C

rs748201105 · VCV2485900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -9.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
Splice region	donor +445	deep intronic (+445 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP -0.75, phastCons 0.13
Non-coding constraint	Z 2.01	1 kb window · o/e 0.85 · regional · uncalibrated
Overall
CADD	14.33	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: CABYR
Coding: c.541+445A>C
MANE Select: NM_153769
dbSNP: rs748201105
Type: single nucleotide variant
Location: chr18:24156487 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.43

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

Similar variants

CABYR c.541+105G>A Uncertain significance ★ ⚠ same type
CABYR c.541+127C>T Uncertain significance ★ ⚠ same type
CABYR c.541+154A>G Uncertain significance ★ ⚠ same type
CABYR c.541+155A>C Uncertain significance ★ ⚠ same type
CABYR c.541+186G>A Uncertain significance ★ ⚠ same type
CABYR c.541+199C>T Uncertain significance ★ ⚠ same type
CABYR c.541+205C>T Uncertain significance ★ ⚠ same type
CABYR c.541+232C>T 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/cabyr-c-541-plus-445a-c (accessed [today's date]).

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