Is CNBD2 p.Asp175Val (c.524A>T) pathogenic?

CNBD2 p.Asp175Val (c.524A>T) is classified Uncertain significance in CNBD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: ambiguous (0.4424); Ultra-rare (popmax 0.029%, eas).

How common is CNBD2 p.Asp175Val (c.524A>T) in the general population?

CNBD2 p.Asp175Val (c.524A>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about CNBD2 p.Asp175Val (c.524A>T)?

AlphaMissense predicts ambiguous (score 0.4424) — an in-silico prediction, not a clinical call.

CNBD2 p.Asp175Val

c.524A>T · VCV3268076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4424 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4424	ambiguous
REVEL	0.244	benign-leaning
SaProt	LLR -9.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.4 · regional, not allelic
Overall
CADD	25.9	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 0.029% East Asian · 13/44,878 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00093% 15/1,613,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
Remaining individualsnot grpmax-eligible	0.0016%	62,466
South Asian	0.0011%	90,940

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.Asp175Val
Coding: c.524A>T
MANE Select: NM_001365709
Type: single nucleotide variant
Location: chr20:35984098 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.79
Residue 175: a binding site

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

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CNBD2 p.Ala88Thr Uncertain significance ★ ⚠ same type
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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-asp175val (accessed [today's date]).

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