Is CACYBP p.Leu55Phe (c.163C>T) pathogenic?

CACYBP p.Leu55Phe (c.163C>T) is classified Uncertain significance in CACYBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0862); Very rare (popmax 0.000424%, nfe).

How common is CACYBP p.Leu55Phe (c.163C>T) in the general population?

CACYBP p.Leu55Phe (c.163C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CACYBP p.Leu55Phe (c.163C>T)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

CACYBP p.Leu55Phe

c.163C>T · rs11548912 · VCV3136562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -8.13	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 -0.1	GERP -1.7
Regional constraint	o/e 0.63	unconstrained · MANE · 9,895 bp · p 1.4e-09 · regional, not allelic
Overall
CADD	13.47	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 0.000424% European (non-Finnish) · 5/1,179,838 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,838 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: CACYBP
Protein: p.Leu55Phe
Coding: c.163C>T
MANE Select: NM_014412
dbSNP: rs11548912
Type: single nucleotide variant
Location: chr1:175004761 (GRCh38)
Gene constraint: LOEUF 1.441 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.05 · 3 PDB
Residue 55: the 'interaction with siah1' region

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

Similar variants

CACYBP p.Thr109= Benign ★★ same type
CACYBP p.Arg208Gln Uncertain significance ★ ⚠ same type
CACYBP p.Arg26Gly Uncertain significance ★ ⚠ same type
CACYBP p.Gln7His Uncertain significance ★ ⚠ same type
CACYBP p.Glu184Gly Uncertain significance ★ ⚠ same type
CACYBP p.Glu227Gly Uncertain significance ★ ⚠ same type
CACYBP p.Ile152Thr Uncertain significance ★ ⚠ same type
CACYBP p.Leu120Pro 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/cacybp-p-leu55phe (accessed [today's date]).

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