Is CNTN1 p.His30= (c.90T>C) pathogenic?

CNTN1 p.His30= (c.90T>C) is classified Benign in CNTN1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.41%, nfe); Associated with Compton-North congenital myopathy.

What condition is associated with CNTN1 p.His30= (c.90T>C)?

CNTN1 p.His30= (c.90T>C) is associated with Compton-North congenital myopathy (ClinVar).

How common is CNTN1 p.His30= (c.90T>C) in the general population?

CNTN1 p.His30= (c.90T>C) is low-frequency (popmax 1.41%, 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.His30=

c.90T>C · rs61748365 · VCV258204

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.41%, nfe)

Conditions

Compton-North congenital myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.79	GERP 1.7, phastCons 1
Overall
CADD	8.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.41% European (non-Finnish) · 16,530/1,172,776 alleles

Filtering AF 1.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.38%

Overall 1.11% 17,776/1,605,248 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.41%	71
Remaining individualsnot grpmax-eligible	0.957%	105
Admixed American	0.313%	319
African / African-American	0.234%	428
Middle Eastern	0.199%	501
Ashkenazi Jewishnot grpmax-eligible	0.193%	517
South Asian	0.161%	622
Finnishnot grpmax-eligible	0.115%	870

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.His30=
Coding: c.90T>C
MANE Select: NM_001843
dbSNP: rs61748365
Type: single nucleotide variant
Location: chr12:40910101 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.29 · 2 PDB

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

F3 p.Ala30Thr Uncertain significance ★ ⚠ same residue
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

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-his30 (accessed [today's date]).

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