Is CNTNAP1 p.Pro1359= (c.4077A>C) pathogenic?

CNTNAP1 p.Pro1359= (c.4077A>C) is classified Likely benign in CNTNAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-11). Ultra-rare (popmax 0.0136%, afr); Associated with CNTNAP1-related disorder.

What condition is associated with CNTNAP1 p.Pro1359= (c.4077A>C)?

CNTNAP1 p.Pro1359= (c.4077A>C) is associated with CNTNAP1-related disorder (ClinVar).

How common is CNTNAP1 p.Pro1359= (c.4077A>C) in the general population?

CNTNAP1 p.Pro1359= (c.4077A>C) is ultra-rare (popmax 0.0136%, afr) (gnomAD).

CNTNAP1 p.Pro1359=

c.4077A>C · rs1299341199 · VCV3030372

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, afr)

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 -1.1	GERP -3
Overall
CADD	0.975	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% African / African-American · 7/51,550 alleles

Filtering AF 0.00632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00451%

Overall 0.00252% 33/1,307,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0136%	7,364
East Asian	0.0126%	7,962
Finnishnot grpmax-eligible	0.0101%	9,937
Admixed American	0.00432%	23,135
South Asian	0.00364%	27,451
Remaining individualsnot grpmax-eligible	0.00215%	46,594
European (non-Finnish)	0.0014%	71,564

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.Pro1359=
Coding: c.4077A>C
MANE Select: NM_003632
dbSNP: rs1299341199
Type: single nucleotide variant
Location: chr17:42698832 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 1359: 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.Pro1320= 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-pro1359 (accessed [today's date]).

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