Is CNBD2 p.Arg234Trp (c.700C>T) pathogenic?

CNBD2 p.Arg234Trp (c.700C>T) is classified Uncertain significance in CNBD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely benign (0.2159); Ultra-rare (popmax 0.0171%, nfe).

How common is CNBD2 p.Arg234Trp (c.700C>T) in the general population?

CNBD2 p.Arg234Trp (c.700C>T) is ultra-rare (popmax 0.0171%, nfe) (gnomAD).

What do computational predictors say about CNBD2 p.Arg234Trp (c.700C>T)?

AlphaMissense predicts likely benign (score 0.2159) — an in-silico prediction, not a clinical call.

CNBD2 p.Arg234Trp

c.700C>T · VCV3494283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2159	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -14.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.8	GERP 1.8, phastCons 0.56
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.4 · regional, not allelic
Overall
CADD	26.4	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 0.0171% European (non-Finnish) · 202/1,180,000 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.0136% 220/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0171%	5,842
Middle Eastern	0.0165%	6,062
South Asian	0.011%	9,107
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00267%	37,515
Admixed American	0.00167%	60,002

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.Arg234Trp
Coding: c.700C>T
MANE Select: NM_001365709
Type: single nucleotide variant
Location: chr20:35984762 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 234: a binding site

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-arg234trp (accessed [today's date]).

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