Is CTNND2 p.Pro7Leu (c.20C>T) pathogenic?

CTNND2 p.Pro7Leu (c.20C>T) is classified Uncertain significance in CTNND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0947); Very rare (popmax 0.00732%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTNND2 p.Pro7Leu (c.20C>T)?

CTNND2 p.Pro7Leu (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTNND2 p.Pro7Leu (c.20C>T) in the general population?

CTNND2 p.Pro7Leu (c.20C>T) is very rare (popmax 0.00732%, afr) (gnomAD).

What do computational predictors say about CTNND2 p.Pro7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

CTNND2 p.Pro7Leu

c.20C>T · VCV4616708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00732%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.82	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 7.9	GERP -0.13, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 557 kb · p 0.95 · regional, not allelic
Overall
CADD	21.4	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 0.00732% African / African-American · 5/68,344 alleles

Filtering AF 0.00284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00185%

Overall 0.000607% 9/1,482,420 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00732%	13,669
Admixed American	0.00228%	43,946
Finnishnot grpmax-eligible	0.00226%	44,240
European (non-Finnish)	0.000178%	561,419

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: CTNND2
Protein: p.Pro7Leu
Coding: c.20C>T
MANE Select: NM_001332
Type: single nucleotide variant
Location: chr5:11903834 (GRCh38)
Gene constraint: LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.88
Residue 7: the 'disordered' region

Full CTNND2 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

CTNND2 p.Asp700Gly Uncertain significance ★★ ⚠ same condition
CTNND2 p.Asp802Asn Uncertain significance ★★ ⚠ same condition
CTNND2 p.Glu217Asp Uncertain significance ★★ ⚠ same condition
CTNND2 p.Ala251Thr Benign/Likely benign ★★ ⚠ same condition
CTNND2 p.Arg427Cys Likely benign ★★ ⚠ same condition
CTNND2 p.Arg454Cys Likely benign ★★ ⚠ same condition
CTNND2 p.Glu26Gln Benign/Likely benign ★★ same condition
CTNND2 p.Gly1104Ser Benign/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/ctnnd2-p-pro7leu (accessed [today's date]).

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