Is CNTNAP1 p.Cys496Trp (c.1488C>G) pathogenic?

CNTNAP1 p.Cys496Trp (c.1488C>G) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1.

How common is CNTNAP1 p.Cys496Trp (c.1488C>G) in the general population?

CNTNAP1 p.Cys496Trp (c.1488C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNTNAP1 p.Cys496Trp (c.1488C>G)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Cys496Trp

c.1488C>G · rs2543794310 · VCV1719485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic · top 2% in CNTNAP1
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	28.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNTNAP1
Protein: p.Cys496Trp
Coding: c.1488C>G
MANE Select: NM_003632
dbSNP: rs2543794310
Type: single nucleotide variant
Location: chr17:42688907 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 496: the laminin g-like 2 domain

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

Similar variants

CNTNAP1 p.Arg1121Ter Pathogenic ★★ same type
CNTNAP1 p.Arg618Ter Pathogenic/Likely pathogenic ★★ same type
CNTNAP1 p.Arg697Ter Pathogenic/Likely pathogenic ★★ same type
CNTNAP1 p.Arg835Ter Pathogenic ★★ same type
CNTNAP1 p.Arg890Ter Pathogenic ★★ same type
CNTNAP1 p.Trp672Ter Pathogenic ★★ same type
CNTNAP1 c.3568+10G>A Uncertain significance ★★ same type
CNTNAP1 p.Ala1322Thr Uncertain significance ★★ ⚠ same type

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-cys496trp (accessed [today's date]).

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