Is CNTNAP1 p.Arg51= (c.151A>C) pathogenic?

CNTNAP1 p.Arg51= (c.151A>C) is classified Benign in CNTNAP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 67.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with lethal congenital contracture syndrome 7.

What condition is associated with CNTNAP1 p.Arg51= (c.151A>C)?

CNTNAP1 p.Arg51= (c.151A>C) is associated with lethal congenital contracture syndrome 7, neuropathy, congenital hypomyelinating, 3 (ClinVar).

CNTNAP1 p.Arg51=

Q: How common is CNTNAP1 p.Arg51= (c.151A>C) in the general population?

CNTNAP1 p.Arg51= (c.151A>C) is common (popmax 67.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.151A>C · rs2271029 · VCV803394

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 67.9%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

lethal congenital contracture syndrome 7

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 4.1	GERP 0.44, phastCons 1
Overall
CADD	13.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 67.9% South Asian · 61,856/91,060 alleles

Filtering AF 67.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.3%

Overall 60.8% 980,732/1,613,058 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	67.9%	1
Finnishnot grpmax-eligible	63.7%	2
European (non-Finnish)	61.6%	2
Remaining individualsnot grpmax-eligible	59.3%	2
African / African-American	59.3%	2
Admixed American	54.4%	2
Amishnot grpmax-eligible	54.3%	2
Middle Eastern	51%	2
East Asian	46%	2
Ashkenazi Jewishnot grpmax-eligible	44.9%	2

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.Arg51=
Coding: c.151A>C
MANE Select: NM_003632
dbSNP: rs2271029
Type: single nucleotide variant
Location: chr17:42683904 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 51: 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

lethal congenital contracture syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuropathy, congenital hypomyelinating, 3

Similar variants

CNTNAP1 p.Arg1121Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg697Ter Pathogenic/Likely pathogenic ★★ same condition
CNTNAP1 p.Arg835Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg890Ter Pathogenic ★★ same condition
CNTNAP1 p.Trp672Ter Pathogenic ★★ same condition
CNTNAP1 p.Arg1073His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg1187His Uncertain significance ★★ ⚠ same condition
CNTNAP1 p.Arg839Trp 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-arg51 (accessed [today's date]).

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