Is CLDND2 p.Ser156Arg (c.468C>A) pathogenic?

CLDND2 p.Ser156Arg (c.468C>A) is classified Uncertain significance in CLDND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.8075); Absent from gnomAD v4.1.

How common is CLDND2 p.Ser156Arg (c.468C>A) in the general population?

CLDND2 p.Ser156Arg (c.468C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLDND2 p.Ser156Arg (c.468C>A)?

AlphaMissense predicts likely pathogenic (score 0.8075) — an in-silico prediction, not a clinical call.

CLDND2 p.Ser156Arg

c.468C>A · VCV4229633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8075 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8075	likely pathogenic · top 5% in CLDND2
REVEL	0.424	indeterminate
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.086, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,432 bp · p 0.36 · regional, not allelic
Overall
CADD	20.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLDND2
Protein: p.Ser156Arg
Coding: c.468C>A
MANE Select: NM_152353
Type: single nucleotide variant
Location: chr19:51367178 (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-ser156arg (accessed [today's date]).

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