Is CACUL1 p.Pro152Ser (c.454C>T) pathogenic?

CACUL1 p.Pro152Ser (c.454C>T) is classified Uncertain significance in CACUL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: ambiguous (0.5331); Very rare (popmax 0.00133%, afr).

How common is CACUL1 p.Pro152Ser (c.454C>T) in the general population?

CACUL1 p.Pro152Ser (c.454C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CACUL1 p.Pro152Ser (c.454C>T)?

AlphaMissense predicts ambiguous (score 0.5331) — an in-silico prediction, not a clinical call.

CACUL1 p.Pro152Ser

c.454C>T · VCV3826802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5331 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.5331	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -7.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 44 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,920 alleles

Overall 0.000124% 2/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,920
European (non-Finnish)	8.48e-05%	1,179,896

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: CACUL1
Protein: p.Pro152Ser
Coding: c.454C>T
MANE Select: NM_153810
Type: single nucleotide variant
Location: chr10:118730324 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 74.25

Full CACUL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACUL1 p.Ala103Thr Uncertain significance ★ ⚠ same type
CACUL1 p.Ala106Thr Uncertain significance ★ ⚠ same type
CACUL1 p.Ala28Gly Uncertain significance ★ ⚠ same type
CACUL1 p.Ala62Glu Uncertain significance ★ ⚠ same type
CACUL1 p.Ala84Asp Uncertain significance ★ ⚠ same type
CACUL1 p.Asp19Asn Uncertain significance ★ ⚠ same type
CACUL1 p.Asp95His Uncertain significance ★ ⚠ same type
CACUL1 p.Gln20Ter 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/cacul1-p-pro152ser (accessed [today's date]).

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