Is CACUL1 p.Ser110Arg (c.330C>G) pathogenic?

CACUL1 p.Ser110Arg (c.330C>G) is classified Uncertain significance in CACUL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.5975); Ultra-rare (popmax 0.046%, sas).

How common is CACUL1 p.Ser110Arg (c.330C>G) in the general population?

CACUL1 p.Ser110Arg (c.330C>G) is ultra-rare (popmax 0.046%, sas) (gnomAD).

What do computational predictors say about CACUL1 p.Ser110Arg (c.330C>G)?

AlphaMissense predicts likely pathogenic (score 0.5975) — an in-silico prediction, not a clinical call.

CACUL1 p.Ser110Arg

c.330C>G · rs200687119 · VCV2269455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5975 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.046%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5975	likely pathogenic
REVEL	0.044	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 366 bp · p 0.0024 · regional, not allelic
Overall
CADD	22.9	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 0.046% South Asian · 41/89,172 alleles

Filtering AF 0.0348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0309%

Overall 0.00732% 117/1,597,644 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.046%	2,175
Remaining individualsnot grpmax-eligible	0.00971%	10,301
European (non-Finnish)	0.0058%	17,256
African / African-American	0.00269%	37,186

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.Ser110Arg
Coding: c.330C>G
MANE Select: NM_153810
dbSNP: rs200687119
Type: single nucleotide variant
Location: chr10:118754433 (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-ser110arg (accessed [today's date]).

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