Is CNTN1 p.Pro762Ala (c.2284C>G) pathogenic?

CNTN1 p.Pro762Ala (c.2284C>G) is classified Uncertain significance in CNTN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-21). AlphaMissense: likely benign (0.1479); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with CNTN1 p.Pro762Ala (c.2284C>G)?

CNTN1 p.Pro762Ala (c.2284C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CNTN1 p.Pro762Ala (c.2284C>G) in the general population?

CNTN1 p.Pro762Ala (c.2284C>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CNTN1 p.Pro762Ala (c.2284C>G)?

AlphaMissense predicts likely benign (score 0.1479) — an in-silico prediction, not a clinical call.

CNTN1 p.Pro762Ala

c.2284C>G · rs566695601 · VCV546503

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1479 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1479	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -6.58	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 7.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 162 kb · p 1.2e-11 · regional, not allelic
Overall
CADD	22.2	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 0.004% African / African-American · 3/74,908 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,966 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: CNTN1
Protein: p.Pro762Ala
Coding: c.2284C>G
MANE Select: NM_001843
dbSNP: rs566695601
Type: single nucleotide variant
Location: chr12:41016781 (GRCh38)
Gene constraint: LOEUF 0.431 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.29 · 2 PDB
Residue 762: the fibronectin type-iii 2 domain

Full CNTN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNTN1 p.Pro762Arg Uncertain significance ★ ⚠ same residue
CNTN1 p.Pro762Ser Uncertain significance ★ ⚠ same residue
CNTN1 p.Ala410Val Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala514Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala528Val Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala668Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala799Thr Uncertain significance ★★ ⚠ same condition
CNTN1 p.Ala930Ser 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/cntn1-p-pro762ala (accessed [today's date]).

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