Is CNTNAP1 p.Ser241Arg (c.723C>G) pathogenic?

CNTNAP1 p.Ser241Arg (c.723C>G) is classified Uncertain significance in CNTNAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). AlphaMissense: likely pathogenic (0.9088); Very rare (popmax 0.00186%, nfe).

How common is CNTNAP1 p.Ser241Arg (c.723C>G) in the general population?

CNTNAP1 p.Ser241Arg (c.723C>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about CNTNAP1 p.Ser241Arg (c.723C>G)?

AlphaMissense predicts likely pathogenic (score 0.9088) — an in-silico prediction, not a clinical call.

CNTNAP1 p.Ser241Arg

c.723C>G · rs756098225 · VCV1908967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9088	likely pathogenic
REVEL	0.496	indeterminate
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.58, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 15 kb · p 9.7e-20 · regional, not allelic
Overall
CADD	21.8	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 0.00186% European (non-Finnish) · 22/1,180,024 alleles

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

Overall 0.00136% 22/1,613,996 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.Ser241Arg
Coding: c.723C>G
MANE Select: NM_003632
dbSNP: rs756098225
Type: single nucleotide variant
Location: chr17:42685964 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.51
Residue 241: the laminin g-like 1 domain

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

Similar variants

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
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-ser241arg (accessed [today's date]).

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