Is CNTNAP1 p.Ala1016Val (c.3047C>T) pathogenic?

CNTNAP1 p.Ala1016Val (c.3047C>T) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-26). AlphaMissense: likely benign (0.1784); Very rare (popmax 0.0022%, sas).

How common is CNTNAP1 p.Ala1016Val (c.3047C>T) in the general population?

CNTNAP1 p.Ala1016Val (c.3047C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CNTNAP1 p.Ala1016Val (c.3047C>T)?

AlphaMissense predicts likely benign (score 0.1784) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Ala1016Val

c.3047C>T · rs145807393 · VCV452906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1784	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -6.50	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 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	22.1	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 0.0022% South Asian · 2/91,092 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00167% 27/1,613,928 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,546
European (non-Finnish)	0.00186%	53,637
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00134%	74,848

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.Ala1016Val
Coding: c.3047C>T
MANE Select: NM_003632
dbSNP: rs145807393
Type: single nucleotide variant
Location: chr17:42695575 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 1016: 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

Similar variants

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CNTNAP1 p.Arg835Ter Pathogenic ★★ same type
CNTNAP1 p.Arg890Ter Pathogenic ★★ same type
CNTNAP1 p.Trp672Ter Pathogenic ★★ same type
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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-ala1016val (accessed [today's date]).

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