Is CUBN p.Ser945Asn (c.2834G>A) pathogenic?

CUBN p.Ser945Asn (c.2834G>A) is classified Uncertain significance in CUBN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.653); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with CUBN p.Ser945Asn (c.2834G>A)?

CUBN p.Ser945Asn (c.2834G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CUBN p.Ser945Asn (c.2834G>A) in the general population?

CUBN p.Ser945Asn (c.2834G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CUBN p.Ser945Asn (c.2834G>A)?

AlphaMissense predicts likely pathogenic (score 0.653) — an in-silico prediction, not a clinical call.

CUBN p.Ser945Asn

c.2834G>A · rs371255463 · VCV2481415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.653	likely pathogenic
REVEL	0.272	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 84 kb · p 0.11 · regional, not allelic
Overall
CADD	23.2	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 0.0011% South Asian · 1/91,070 alleles

Overall 0.000137% 2/1,461,456 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,070
European (non-Finnish)	8.48e-05%	1,179,664

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: CUBN
Protein: p.Ser945Asn
Coding: c.2834G>A
MANE Select: NM_001081
dbSNP: rs371255463
Type: single nucleotide variant
Location: chr10:17068238 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 945: a disulfide bond; the cub 5 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUBN p.Arg2444Ter Pathogenic ★★ same condition
CUBN p.Ala1501Glu Uncertain significance ★★ same condition
CUBN p.Ala2086Thr Uncertain significance ★★ same condition
CUBN p.Ala238Val Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1268Cys Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1345Trp Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1636Trp Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1695His Uncertain significance ★★ same condition

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/cubn-p-ser945asn (accessed [today's date]).

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