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

CABYR c.541+445A>G is classified Uncertain significance in CABYR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely benign (0.0691); Very rare (popmax 0.00167%, amr).

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

CABYR c.541+445A>G is very rare (popmax 0.00167%, amr) (gnomAD).

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

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

CABYR c.541+445A>G

rs748201105 · VCV2293639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -9.37	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	14.52	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 0.00167% Admixed American · 1/59,902 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,680 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,902
African / African-American	0.00133%	74,936
European (non-Finnish)	0.000678%	147,492

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: CABYR
Coding: c.541+445A>G
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-g (accessed [today's date]).

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