Is CNTN1 p.Ala69= (c.207C>T) pathogenic?

CNTN1 p.Ala69= (c.207C>T) is classified Benign/Likely benign in CNTN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-01). Rare (popmax 0.966%, nfe); Associated with Compton-North congenital myopathy.

What condition is associated with CNTN1 p.Ala69= (c.207C>T)?

CNTN1 p.Ala69= (c.207C>T) is associated with Compton-North congenital myopathy (ClinVar).

How common is CNTN1 p.Ala69= (c.207C>T) in the general population?

CNTN1 p.Ala69= (c.207C>T) is rare (popmax 0.966%, nfe) (gnomAD).

How is Congenital lethal myopathy, Compton-North type inherited?

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

CNTN1 p.Ala69=

c.207C>T · rs7297132 · VCV210737

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.966%, nfe)

Conditions

Compton-North congenital myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.75	GERP 1.4, phastCons 1
Overall
CADD	11.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.966% European (non-Finnish) · 11,399/1,179,592 alleles

Filtering AF 0.951% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.945%

Overall 0.796% 12,838/1,613,610 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.08%	48
European (non-Finnish)grpmax	0.966%	103
Ashkenazi Jewishnot grpmax-eligible	0.818%	122
Remaining individualsnot grpmax-eligible	0.738%	136
Admixed American	0.71%	141
Middle Eastern	0.462%	216
African / African-American	0.157%	636
Finnishnot grpmax-eligible	0.109%	915
South Asian	0.0813%	1,231
East Asian	0.00223%	44,862

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: CNTN1
Protein: p.Ala69=
Coding: c.207C>T
MANE Select: NM_001843
dbSNP: rs7297132
Type: single nucleotide variant
Location: chr12:40918751 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.29 · 2 PDB
Residue 69: a disulfide bond; the ig-like c2-type 1 domain

Full CNTN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Compton-North congenital myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital lethal myopathy, Compton-North type (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

CNTN1 p.Ala410Val Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala514Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala528Val Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala668Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala799Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala930Ser Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala995Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Arg274Gln 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/cntn1-p-ala69 (accessed [today's date]).

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