Is CLDND2 p.Ser97Asn (c.290G>A) pathogenic?

CLDND2 p.Ser97Asn (c.290G>A) is classified Uncertain significance in CLDND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.32); Ultra-rare (popmax 0.0227%, afr).

How common is CLDND2 p.Ser97Asn (c.290G>A) in the general population?

CLDND2 p.Ser97Asn (c.290G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about CLDND2 p.Ser97Asn (c.290G>A)?

AlphaMissense predicts likely benign (score 0.32) — an in-silico prediction, not a clinical call.

CLDND2 p.Ser97Asn

c.290G>A · VCV4229630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.32 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.32	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -12.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.3, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 1,432 bp · p 0.36 · regional, not allelic
Overall
CADD	8.258	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 0.0227% African / African-American · 17/75,048 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0018% 29/1,612,192 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,415
Admixed American	0.00834%	11,996
Remaining individualsnot grpmax-eligible	0.00481%	20,807
European (non-Finnish)	0.000339%	294,939

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: CLDND2
Protein: p.Ser97Asn
Coding: c.290G>A
MANE Select: NM_152353
Type: single nucleotide variant
Location: chr19:51367906 (GRCh38)
Gene constraint: LOEUF 1.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.58

Full CLDND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDND2 p.Thr157= Likely benign ★★ same type
CLDND2 p.Ala136Pro Uncertain significance ★ ⚠ same type
CLDND2 p.Ala64Val Uncertain significance ★ ⚠ same type
CLDND2 p.Arg33Cys Uncertain significance ★ ⚠ same type
CLDND2 p.Arg5Trp Uncertain significance ★ ⚠ same type
CLDND2 p.Arg92Gln Uncertain significance ★ ⚠ same type
CLDND2 p.Cys55Phe Uncertain significance ★ ⚠ same type
CLDND2 p.Glu89Lys 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/cldnd2-p-ser97asn (accessed [today's date]).

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