Is CNTNAP1 p.Pro1320= (c.3960C>T) pathogenic?

CNTNAP1 p.Pro1320= (c.3960C>T) is classified Likely benign in CNTNAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-09). Very rare (popmax 0.00525%, nfe); Associated with CNTNAP1-related disorder.

What condition is associated with CNTNAP1 p.Pro1320= (c.3960C>T)?

CNTNAP1 p.Pro1320= (c.3960C>T) is associated with CNTNAP1-related disorder (ClinVar).

How common is CNTNAP1 p.Pro1320= (c.3960C>T) in the general population?

CNTNAP1 p.Pro1320= (c.3960C>T) is very rare (popmax 0.00525%, nfe) (gnomAD).

CNTNAP1 p.Pro1320=

c.3960C>T · rs144975726 · VCV3045193

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Conditions

CNTNAP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 1
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,179,908 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00384% 62/1,613,510 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.Pro1320=
Coding: c.3960C>T
MANE Select: NM_003632
dbSNP: rs144975726
Type: single nucleotide variant
Location: chr17:42698715 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 1320: the 'disordered' region; a UniProt-annotated variant site (in chn3); a UniProt-annotated variant site (in lccs7 and chn3); a UniProt-annotated variant site (in lccs7)

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

Disease context

CNTNAP1-related disorder

Similar variants

CNTNAP1 c.2060-1G>A Likely pathogenic ★ same condition
CNTNAP1 p.Arg270Ter Pathogenic ★ same condition
CNTNAP1 p.Gln1132Ter Likely pathogenic ★ same condition
CNTNAP1 p.Gln671Ter Pathogenic ★ same condition
CNTNAP1 p.Arg1150Ser Uncertain significance ⚠ same condition
CNTNAP1 p.Leu103= Likely benign same condition
CNTNAP1 p.Pro1359= Likely benign same condition
CNTNAP1 p.Tyr104= Likely 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-pro1320 (accessed [today's date]).

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