Is CNTNAP1 p.Tyr482Ter (c.1446T>G) pathogenic?

CNTNAP1 p.Tyr482Ter (c.1446T>G) is classified Likely pathogenic in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). Absent from gnomAD v4.1; Associated with neuropathy, congenital hypomyelinating, 3.

What condition is associated with CNTNAP1 p.Tyr482Ter (c.1446T>G)?

CNTNAP1 p.Tyr482Ter (c.1446T>G) is associated with neuropathy, congenital hypomyelinating, 3 (ClinVar).

How common is CNTNAP1 p.Tyr482Ter (c.1446T>G) in the general population?

CNTNAP1 p.Tyr482Ter (c.1446T>G) is absent from gnomAD v4.1 (gnomAD).

CNTNAP1 p.Tyr482Ter

c.1446T>G · rs2543793851 · VCV2671767

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuropathy, congenital hypomyelinating, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -3.8, phastCons 0.99
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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNTNAP1
Protein: p.Tyr482Ter
Coding: c.1446T>G
MANE Select: NM_003632
dbSNP: rs2543793851
Type: single nucleotide variant
Location: chr17:42688601 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 482: the laminin g-like 2 domain

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

Disease context

neuropathy, congenital hypomyelinating, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNTNAP1 p.Arg1121Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg697Ter Pathogenic/Likely pathogenic ★★ same condition
CNTNAP1 p.Arg835Ter Pathogenic ★★ same condition
CNTNAP1 p.Trp672Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg1073His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1187His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Thr569Met Uncertain significance ★★ ⚠ same condition
CNTNAP1 c.1736-22G>A Benign ★★ 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/cntnap1-p-tyr482ter (accessed [today's date]).

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