Is CDHR2 p.Tyr768= (c.2304C>T) pathogenic?

CDHR2 p.Tyr768= (c.2304C>T) is classified Likely benign in CDHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Ultra-rare (popmax 0.0332%, mid).

How common is CDHR2 p.Tyr768= (c.2304C>T) in the general population?

CDHR2 p.Tyr768= (c.2304C>T) is ultra-rare (popmax 0.0332%, mid) (gnomAD).

CDHR2 p.Tyr768=

c.2304C>T · VCV3905195

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

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 -15	GERP -3.3
Overall
CADD	0.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0332% Middle Eastern · 2/6,028 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00491%

Overall 0.00659% 106/1,607,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,014
Remaining individualsnot grpmax-eligible	0.0129%	7,776
African / African-American	0.012%	8,330
East Asian	0.0112%	8,955
European (non-Finnish)	0.00655%	15,270
South Asian	0.00443%	22,579
Admixed American	0.00167%	59,770

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: CDHR2
Protein: p.Tyr768=
Coding: c.2304C>T
MANE Select: NM_017675
Type: single nucleotide variant
Location: chr5:176584585 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 2 PDB
Residue 768: the cadherin 7 domain

Full CDHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR2 p.Ala1162Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala121Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala13Val Uncertain significance ★ ⚠ same type
CDHR2 p.Ala415Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala423Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala512Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala652Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala656Thr 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/cdhr2-p-tyr768 (accessed [today's date]).

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