Is CNTNAP1 p.Trp61fs (c.180del) pathogenic?

CNTNAP1 p.Trp61fs (c.180del) is classified Pathogenic in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-02). Very rare (popmax 8.47e-05%, nfe).

How common is CNTNAP1 p.Trp61fs (c.180del) in the general population?

CNTNAP1 p.Trp61fs (c.180del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CNTNAP1 p.Trp61fs

c.180del · VCV4734614

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.7	GERP -5
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,974 alleles

Overall 0.000657% 1/152,156 alleles · very rare

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: CNTNAP1
Protein: p.Trp61fs
Coding: c.180del
MANE Select: NM_003632
Type: Deletion
Location: chr17:42684044 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 61: a disulfide bond; the f5/8 type c domain

Full CNTNAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNTNAP1 p.Cys968fs Pathogenic ★★ same type
CNTNAP1 c.1046del Pathogenic ★ same type
CNTNAP1 p.Leu1256fs Pathogenic ★ same type
CNTNAP1 p.Leu608fs Likely pathogenic ★ same type
CNTNAP1 p.Phe177fs Pathogenic ★ same type
CNTNAP1 p.Phe329fs Pathogenic ★ same type
CNTNAP1 c.2993-12_2993-3del Uncertain significance ★ same type
CNTNAP1 p.Gly718del 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/cntnap1-p-trp61fs (accessed [today's date]).

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