Is CNTNAP1 p.Leu103= (c.309C>G) pathogenic?

CNTNAP1 p.Leu103= (c.309C>G) is classified Likely benign in CNTNAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-12). Very rare (popmax 0.00223%, eas); Associated with CNTNAP1-related disorder.

What condition is associated with CNTNAP1 p.Leu103= (c.309C>G)?

CNTNAP1 p.Leu103= (c.309C>G) is associated with CNTNAP1-related disorder (ClinVar).

How common is CNTNAP1 p.Leu103= (c.309C>G) in the general population?

CNTNAP1 p.Leu103= (c.309C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

CNTNAP1 p.Leu103=

c.309C>G · rs752012820 · VCV3047213

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

CNTNAP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.004	GERP 0.38, phastCons 0.79
Overall
CADD	11.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,862 alleles

Overall 0.000137% 2/1,461,818 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,862
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Leu103=
Coding: c.309C>G
MANE Select: NM_003632
dbSNP: rs752012820
Type: single nucleotide variant
Location: chr17:42684175 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 103: a disulfide bond; the f5/8 type c domain

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

Disease context

CNTNAP1-related disorder

Similar variants

CNTNAP1 c.2060-1G>A Likely pathogenic ★ same condition
CNTNAP1 p.Arg270Ter Pathogenic ★ same condition
CNTNAP1 p.Gln1132Ter Likely pathogenic ★ same condition
CNTNAP1 p.Gln671Ter Pathogenic ★ same condition
CNTNAP1 p.Arg1150Ser Uncertain significance ⚠ same condition
CNTNAP1 p.Pro1320= Likely benign same condition
CNTNAP1 p.Pro1359= Likely benign same condition
CNTNAP1 p.Tyr104= Likely benign 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-leu103 (accessed [today's date]).

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