Is CNTNAP1 p.Arg890Ter (c.2668C>T) pathogenic?

CNTNAP1 p.Arg890Ter (c.2668C>T) is classified Pathogenic in CNTNAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-17). Very rare (popmax 0.00267%, afr); Associated with lethal congenital contracture syndrome 7.

What condition is associated with CNTNAP1 p.Arg890Ter (c.2668C>T)?

CNTNAP1 p.Arg890Ter (c.2668C>T) is associated with lethal congenital contracture syndrome 7 (ClinVar).

How common is CNTNAP1 p.Arg890Ter (c.2668C>T) in the general population?

CNTNAP1 p.Arg890Ter (c.2668C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

CNTNAP1 p.Arg890Ter

c.2668C>T · rs144659252 · VCV692016

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

lethal congenital contracture syndrome 7

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 17 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Overall
CADD	38.0	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 0.00267% African / African-American · 2/74,932 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000743% 12/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,466
European (non-Finnish)	0.000847%	118,006

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.Arg890Ter
Coding: c.2668C>T
MANE Select: NM_003632
dbSNP: rs144659252
Type: single nucleotide variant
Location: chr17:42692636 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 890: the laminin g-like 3 domain; 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

lethal congenital contracture syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNTNAP1 p.Arg890Gln Uncertain significance ★ ⚠ same residue
CNTNAP1 p.Arg1121Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg839Trp Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg977His Uncertain significance ★★ ⚠ same condition
CNTNAP1 c.1736-22G>A Benign ★★ same condition
CNTNAP1 c.364-34A>G Benign ★★ same condition
CNTNAP1 p.Arg51= Benign ★★ same condition
CNTNAP1 p.Asp109= Benign/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-arg890ter (accessed [today's date]).

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