Is CUBN p.Ser1952= (c.5856A>G) pathogenic?

CUBN p.Ser1952= (c.5856A>G) is classified Benign in CUBN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 70.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Imerslund-Grasbeck syndrome type 1.

What condition is associated with CUBN p.Ser1952= (c.5856A>G)?

CUBN p.Ser1952= (c.5856A>G) is associated with Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome (ClinVar).

How is Imerslund-Gräsbeck syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CUBN p.Ser1952=

Q: How common is CUBN p.Ser1952= (c.5856A>G) in the general population?

CUBN p.Ser1952= (c.5856A>G) is common (popmax 70.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5856A>G · rs1801234 · VCV299453

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 70.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Imerslund-Grasbeck syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.77	GERP -3.1, phastCons 0.02
Overall
CADD	0.714	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.5% African / African-American · 52,767/74,878 alleles

Filtering AF 70% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.8%

Overall 44.4% 716,573/1,612,408 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	70.5%	1
Admixed American	57.9%	2
East Asian	52.7%	2
Remaining individualsnot grpmax-eligible	44.7%	2
South Asian	44.1%	2
European (non-Finnish)	42.4%	2
Finnishnot grpmax-eligible	39.2%	3
Middle Eastern	36.1%	3
Amishnot grpmax-eligible	34.3%	3
Ashkenazi Jewishnot grpmax-eligible	33.9%	3

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.Ser1952=
Coding: c.5856A>G
MANE Select: NM_001081
dbSNP: rs1801234
Type: single nucleotide variant
Location: chr10:16937662 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1952: a UniProt-annotated variant site (in prochob); the cub 13 domain

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

Disease context

Imerslund-Grasbeck syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Imerslund-Grasbeck syndrome

For Imerslund-Gräsbeck syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Finland)

Similar variants

CUBN c.10033-1G>A Likely pathogenic ★★ same condition
CUBN c.1230+1G>A Pathogenic/Likely pathogenic ★★ same condition
CUBN c.3672+2T>C Likely pathogenic ★★ same condition
CUBN c.3829+1G>A Pathogenic/Likely pathogenic ★★ same condition
CUBN c.4350+2T>C Likely pathogenic ★★ same condition
CUBN c.6821+3A>G Pathogenic/Likely pathogenic ★★ same condition
CUBN c.6822-1G>A Likely pathogenic ★★ same condition
CUBN c.8598+1G>T Likely pathogenic ★★ 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-ser1952 (accessed [today's date]).

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