Is CNTNAP1 p.Pro473Ser (c.1417C>T) pathogenic?

CNTNAP1 p.Pro473Ser (c.1417C>T) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-12). AlphaMissense: ambiguous (0.3896); Very rare (popmax 0.00223%, eas).

How common is CNTNAP1 p.Pro473Ser (c.1417C>T) in the general population?

CNTNAP1 p.Pro473Ser (c.1417C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CNTNAP1 p.Pro473Ser (c.1417C>T)?

AlphaMissense predicts ambiguous (score 0.3896) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Pro473Ser

c.1417C>T · rs146616808 · VCV2683419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.3896	ambiguous
REVEL	0.442	indeterminate
SaProt	LLR -3.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0013% 21/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
European (non-Finnish)	0.00169%	59,002

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.Pro473Ser
Coding: c.1417C>T
MANE Select: NM_003632
dbSNP: rs146616808
Type: single nucleotide variant
Location: chr17:42688572 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 473: the laminin g-like 2 domain

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

Similar variants

CNTNAP1 p.Pro473Ala Uncertain significance ★★ ⚠ same residue
CNTNAP1 p.Pro473Leu Uncertain significance ★ ⚠ same residue
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

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-pro473ser (accessed [today's date]).

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