Is CNTNAP1 p.Cys968fs (c.2901_2902del) pathogenic?

CNTNAP1 p.Cys968fs (c.29012902del) is classified Pathogenic in CNTNAP1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-03-29). Very rare (popmax 0.00891%, eas); Associated with neuropathy, congenital hypomyelinating, 3.

What condition is associated with CNTNAP1 p.Cys968fs (c.2901_2902del)?

CNTNAP1 p.Cys968fs (c.2901_2902del) is associated with neuropathy, congenital hypomyelinating, 3, lethal congenital contracture syndrome 7 (ClinVar).

How common is CNTNAP1 p.Cys968fs (c.2901_2902del) in the general population?

CNTNAP1 p.Cys968fs (c.2901_2902del) is very rare (popmax 0.00891%, eas) (gnomAD).

CNTNAP1 p.Cys968fs

c.2901_2902del · rs751050956 · VCV204313

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

neuropathy, congenital hypomyelinating, 3

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 18 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 0.62, phastCons 1
Overall
CADD	34.0	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 0.00891% East Asian · 4/44,888 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00217% 35/1,614,120 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
African / African-American	0.00534%	18,734
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Finnishnot grpmax-eligible	0.00312%	32,017
South Asian	0.0022%	45,547
European (non-Finnish)	0.00169%	59,003

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.Cys968fs
Coding: c.2901_2902del
MANE Select: NM_003632
dbSNP: rs751050956
Type: Deletion
Location: chr17:42693445 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 968: the egf-like 2 domain; a disulfide bond; 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

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

Also linked: lethal congenital contracture syndrome 7

Similar variants

CNTNAP1 p.Leu608fs Likely pathogenic ★ same condition
CNTNAP1 p.Phe177fs Pathogenic ★ same condition
CNTNAP1 p.Gly718del Uncertain significance ★ same condition
CNTNAP1 c.2993-1_2995del Pathogenic same condition
CNTNAP1 p.Arg1121Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg697Ter Pathogenic/Likely pathogenic ★★ same condition
CNTNAP1 p.Arg835Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg890Ter Pathogenic ★★ 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-cys968fs (accessed [today's date]).

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