Is CDH2 p.Asn845Ser (c.2534A>G) pathogenic?

CDH2 p.Asn845Ser (c.2534A>G) is classified Benign/Likely benign in CDH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0807); Low-frequency (popmax 4.84%, sas).

How common is CDH2 p.Asn845Ser (c.2534A>G) in the general population?

CDH2 p.Asn845Ser (c.2534A>G) is low-frequency (popmax 4.84%, sas) (gnomAD).

What do computational predictors say about CDH2 p.Asn845Ser (c.2534A>G)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

CDH2 p.Asn845Ser

c.2534A>G · rs2289664 · VCV1566047

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.84%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -4.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 0.01 · regional, not allelic
Overall
CADD	22.1	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 4.84% South Asian · 4,405/91,052 alleles

Filtering AF 4.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.67%

Overall 2.73% 44,003/1,613,268 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.84%	21
Middle Eastern	4.25%	24
European (non-Finnish)	2.84%	35
Remaining individualsnot grpmax-eligible	2.75%	36
Ashkenazi Jewishnot grpmax-eligible	2.63%	38
Finnishnot grpmax-eligible	2.46%	41
Admixed American	1.52%	66
East Asian	1.14%	87
Amishnot grpmax-eligible	0.877%	114
African / African-American	0.427%	234

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: CDH2
Protein: p.Asn845Ser
Coding: c.2534A>G
MANE Select: NM_001792
dbSNP: rs2289664
Type: single nucleotide variant
Location: chr18:27952340 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68
Residue 845: a UniProt-annotated variant site (in)

Full CDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH2 c.1344+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH2 c.702+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH2 p.Tyr676Cys Pathogenic ★★ same type
CDH2 c.61-1G>A Uncertain significance ★★ same type
CDH2 c.848-16T>G Uncertain significance ★★ same type
CDH2 p.Ala106Val Uncertain significance ★★ ⚠ same type
CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same type
CDH2 p.Ala294Gly 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/cdh2-p-asn845ser (accessed [today's date]).

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