Is CUBN p.Phe1716= (c.5148C>T) pathogenic?

CUBN p.Phe1716= (c.5148C>T) is classified Benign/Likely benign in CUBN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-03). Rare (popmax 0.301%, eas); Associated with Imerslund-Grasbeck syndrome type 1.

What condition is associated with CUBN p.Phe1716= (c.5148C>T)?

CUBN p.Phe1716= (c.5148C>T) is associated with Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome, proteinuria, chronic benign (ClinVar).

How common is CUBN p.Phe1716= (c.5148C>T) in the general population?

CUBN p.Phe1716= (c.5148C>T) is rare (popmax 0.301%, eas) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

CUBN p.Phe1716=

c.5148C>T · rs370581324 · VCV880317

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.301%, eas)

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 -0.071	GERP -3.4
Overall
CADD	4.539	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.301% East Asian · 135/44,864 alleles

Filtering AF 0.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0139% 225/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.301%	332
South Asian	0.0307%	3,253
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.00833%	12,004
European (non-Finnish)	0.00381%	26,222
African / African-American	0.00133%	75,054

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.Phe1716=
Coding: c.5148C>T
MANE Select: NM_001081
dbSNP: rs370581324
Type: single nucleotide variant
Location: chr10:16948539 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1716: a UniProt-annotated variant site (in prochob); the cub 11 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 proteinuria, chronic benign

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-phe1716 (accessed [today's date]).

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