Is CNBD2 p.Lys413Asn (c.1239G>T) pathogenic?

CNBD2 p.Lys413Asn (c.1239G>T) is classified Uncertain significance in CNBD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.7173); Ultra-rare (popmax 0.0527%, afr).

How common is CNBD2 p.Lys413Asn (c.1239G>T) in the general population?

CNBD2 p.Lys413Asn (c.1239G>T) is ultra-rare (popmax 0.0527%, afr) (gnomAD).

What do computational predictors say about CNBD2 p.Lys413Asn (c.1239G>T)?

AlphaMissense predicts likely pathogenic (score 0.7173) — an in-silico prediction, not a clinical call.

CNBD2 p.Lys413Asn

c.1239G>T · VCV4230661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7173 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7173	likely pathogenic · top 8% in CNBD2
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.4 · regional, not allelic
Overall
CADD	18.28	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 0.0527% African / African-American · 39/73,988 alleles

Filtering AF 0.0396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.00271% 43/1,587,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0527%	1,897
Remaining individualsnot grpmax-eligible	0.00489%	20,433
Admixed American	0.00176%	56,868

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: CNBD2
Protein: p.Lys413Asn
Coding: c.1239G>T
MANE Select: NM_001365709
Type: single nucleotide variant
Location: chr20:36011227 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.79

Full CNBD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNBD2 p.Ala121Thr Uncertain significance ★ ⚠ same type
CNBD2 p.Ala566Gly Uncertain significance ★ ⚠ same type
CNBD2 p.Ala566Thr Uncertain significance ★ ⚠ same type
CNBD2 p.Ala576Thr Uncertain significance ★ ⚠ same type
CNBD2 p.Ala88Thr Uncertain significance ★ ⚠ same type
CNBD2 p.Arg118Trp Uncertain significance ★ ⚠ same type
CNBD2 p.Arg133Cys Uncertain significance ★ ⚠ same type
CNBD2 p.Arg133His 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/cnbd2-p-lys413asn (accessed [today's date]).

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