Is CNBP p.Asp52= (c.156C>T) pathogenic?

CNBP p.Asp52= (c.156C>T) is classified Benign in CNBP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-22). Common (popmax 97.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with myotonic dystrophy type 2.

What condition is associated with CNBP p.Asp52= (c.156C>T)?

CNBP p.Asp52= (c.156C>T) is associated with myotonic dystrophy type 2 (ClinVar).

How is Proximal myotonic myopathy inherited?

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

CNBP p.Asp52=

Q: How common is CNBP p.Asp52= (c.156C>T) in the general population?

CNBP p.Asp52= (c.156C>T) is common (popmax 97.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.156C>T · rs4303883 · VCV1217358

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 97.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

myotonic dystrophy type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 97.5% European (non-Finnish) · 1,150,152/1,179,970 alleles

Filtering AF 97.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 97.3%

Overall 93.3% 1,506,588/1,614,018 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	99.7%	1
European (non-Finnish)grpmax	97.5%	1
Finnishnot grpmax-eligible	95.6%	1
Ashkenazi Jewishnot grpmax-eligible	95.5%	1
Remaining individualsnot grpmax-eligible	91.8%	1
East Asian	90.8%	1
Middle Eastern	89.2%	1
Admixed American	87.6%	1
South Asian	85.7%	1
African / African-American	42.5%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CNBP
Protein: p.Asp52=
Coding: c.156C>T
MANE Select: NM_003418
dbSNP: rs4303883
Type: single nucleotide variant
Location: chr3:129171507 (GRCh38)
Gene constraint: LOEUF 0.541 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 71.09

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

Disease context

myotonic dystrophy type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Proximal myotonic myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Elderly
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

CNBP p.Asp52Glu Uncertain significance ★ ⚠ same residue
CNBP c.-14-833_-14-806CCTG[(75_11000 Pathogenic same condition
CNBP p.Asn100Ser Uncertain significance ★ ⚠ same type
CNBP p.Cys122Ser Uncertain significance ★ ⚠ same type
CNBP p.Glu5Asp Uncertain significance ★ ⚠ same type
CNBP p.Gly36Cys Uncertain significance ★ ⚠ same type
CNBP p.His113Arg Uncertain significance ★ ⚠ same type
CNBP p.Pro104Ala 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/cnbp-p-asp52 (accessed [today's date]).

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