Is CNTNAP1 p.Ala17Val (c.50C>T) pathogenic?

CNTNAP1 p.Ala17Val (c.50C>T) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-07). AlphaMissense: likely benign (0.1051); Ultra-rare (popmax 0.0187%, afr).

How common is CNTNAP1 p.Ala17Val (c.50C>T) in the general population?

CNTNAP1 p.Ala17Val (c.50C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about CNTNAP1 p.Ala17Val (c.50C>T)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Ala17Val

c.50C>T · rs537059106 · VCV1964702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,091 bp · p 0.69 · regional, not allelic
Overall
CADD	18.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,786 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00906%

Overall 0.000999% 16/1,601,348 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,342
Admixed American	0.00171%	58,504
Remaining individualsnot grpmax-eligible	0.00161%	61,934

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.Ala17Val
Coding: c.50C>T
MANE Select: NM_003632
dbSNP: rs537059106
Type: single nucleotide variant
Location: chr17:42682879 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51

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-ala17val (accessed [today's date]).

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