Is CNTNAP1 p.Pro1196= (c.3588G>A) pathogenic?

CNTNAP1 p.Pro1196= (c.3588G>A) is classified Likely benign in CNTNAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Rare (popmax 0.182%, nfe).

How common is CNTNAP1 p.Pro1196= (c.3588G>A) in the general population?

CNTNAP1 p.Pro1196= (c.3588G>A) is rare (popmax 0.182%, nfe) (gnomAD).

CNTNAP1 p.Pro1196=

c.3588G>A · rs142952244 · VCV773752

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.182%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.8	GERP -5
Overall
CADD	1.715	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.182% European (non-Finnish) · 2,149/1,179,982 alleles

Filtering AF 0.176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.157% 2,526/1,613,990 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.5%	200
European (non-Finnish)grpmax	0.182%	549
Finnishnot grpmax-eligible	0.161%	622
Remaining individualsnot grpmax-eligible	0.149%	672
Middle Eastern	0.033%	3,031
Admixed American	0.0183%	5,454
African / African-American	0.0173%	5,765
South Asian	0.00549%	18,215
East Asian	0.00446%	22,438

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1196=
Coding: c.3588G>A
MANE Select: NM_003632
dbSNP: rs142952244
Type: single nucleotide variant
Location: chr17:42697573 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 1196: the laminin g-like 4 domain; 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

CNTNAP1 p.Pro1196Thr 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
CNTNAP1 c.3568+10G>A 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-pro1196 (accessed [today's date]).

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