Is CDH2 p.Ala77= (c.231A>T) pathogenic?

CDH2 p.Ala77= (c.231A>T) is classified Likely benign in CDH2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.0218%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDH2 p.Ala77= (c.231A>T)?

CDH2 p.Ala77= (c.231A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH2 p.Ala77= (c.231A>T) in the general population?

CDH2 p.Ala77= (c.231A>T) is ultra-rare (popmax 0.0218%, nfe) (gnomAD).

CDH2 p.Ala77=

c.231A>T · rs148115828 · VCV1567207

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0218%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.95	GERP -1, phastCons 0.005
Overall
CADD	6.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0218% European (non-Finnish) · 257/1,179,956 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.0172% 278/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0218%	4,591
Middle Eastern	0.0165%	6,062
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Finnishnot grpmax-eligible	0.00156%	63,966
African / African-American	0.00133%	75,052

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.Ala77=
Coding: c.231A>T
MANE Select: NM_001792
dbSNP: rs148115828
Type: single nucleotide variant
Location: chr18:28013851 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH2 p.Ala77Ser Uncertain significance ★ ⚠ same residue
CDH2 p.Ala77Glu Uncertain significance ★ ⚠ same residue
CDH2 p.Ala77Thr Uncertain significance ★ ⚠ same residue
CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala294Gly Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala415Ser Uncertain significance ★★ ⚠ same condition
CDH2 p.Ala418Ser Uncertain significance ★★ ⚠ same condition

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-ala77 (accessed [today's date]).

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