Is CNTNAP1 p.Arg802Cys (c.2404C>T) pathogenic?

CNTNAP1 p.Arg802Cys (c.2404C>T) is classified Uncertain significance in CNTNAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-07). AlphaMissense: ambiguous (0.4869); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with CNTNAP1 p.Arg802Cys (c.2404C>T)?

CNTNAP1 p.Arg802Cys (c.2404C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CNTNAP1 p.Arg802Cys (c.2404C>T) in the general population?

CNTNAP1 p.Arg802Cys (c.2404C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CNTNAP1 p.Arg802Cys (c.2404C>T)?

AlphaMissense predicts ambiguous (score 0.4869) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Arg802Cys

c.2404C>T · rs777914248 · VCV1901150

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4869	ambiguous
REVEL	0.463	indeterminate
SaProt	LLR -7.82	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00266% 43/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,811
South Asiangrpmax	0.00329%	30,361
European (non-Finnish)	0.00254%	39,335
East Asian	0.00223%	44,898
Finnishnot grpmax-eligible	0.00156%	64,038

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg802Cys
Coding: c.2404C>T
MANE Select: NM_003632
dbSNP: rs777914248
Type: single nucleotide variant
Location: chr17:42691865 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 802: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNTNAP1 p.Arg802His Uncertain significance ★ ⚠ same residue
CNTNAP1 p.Ala1322Thr Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Ala254Thr Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Ala40Thr Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Ala887Val Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1022Ser Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1073His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1150Cys Uncertain significance ★★ ⚠ 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-arg802cys (accessed [today's date]).

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