Is CNTNAP1 p.Ala947Val (c.2840C>T) pathogenic?

CNTNAP1 p.Ala947Val (c.2840C>T) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: ambiguous (0.3922); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CNTNAP1 p.Ala947Val (c.2840C>T)?

CNTNAP1 p.Ala947Val (c.2840C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CNTNAP1 p.Ala947Val (c.2840C>T) in the general population?

CNTNAP1 p.Ala947Val (c.2840C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CNTNAP1 p.Ala947Val (c.2840C>T)?

AlphaMissense predicts ambiguous (score 0.3922) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Ala947Val

c.2840C>T · rs754503459 · VCV2340869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3922	ambiguous
REVEL	0.501	indeterminate
SaProt	LLR -10.89	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	24.3	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 0.000169% European (non-Finnish) · 2/1,180,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,890 alleles · very rare

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.Ala947Val
Coding: c.2840C>T
MANE Select: NM_003632
dbSNP: rs754503459
Type: single nucleotide variant
Location: chr17:42693384 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 947: the laminin g-like 3 domain; a disulfide bond; 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.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
CNTNAP1 p.Arg1153Gln 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-ala947val (accessed [today's date]).

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