Is CDHR1 p.Glu680Ter (c.2038G>T) pathogenic?

CDHR1 p.Glu680Ter (c.2038G>T) is classified Pathogenic/Likely pathogenic in CDHR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-30). Very rare (popmax 0.000254%, nfe); Associated with CDHR1-related disorders.

What condition is associated with CDHR1 p.Glu680Ter (c.2038G>T)?

CDHR1 p.Glu680Ter (c.2038G>T) is associated with CDHR1-related disorders (ClinVar).

How common is CDHR1 p.Glu680Ter (c.2038G>T) in the general population?

CDHR1 p.Glu680Ter (c.2038G>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

CDHR1 p.Glu680Ter

c.2038G>T · rs2492544964 · VCV2008868

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

CDHR1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (16 of 17, 2 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 4.6, phastCons 1
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,044 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,838 alleles · very rare

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: CDHR1
Protein: p.Glu680Ter
Coding: c.2038G>T
MANE Select: NM_033100
dbSNP: rs2492544964
Type: single nucleotide variant
Location: chr10:84213346 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 680: the cadherin 6 domain

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDHR1-related disorders

Similar variants

CDHR1 c.1168-1G>C Pathogenic/Likely pathogenic ★★ same condition
CDHR1 c.1321-1G>A Likely pathogenic ★★ same condition
CDHR1 c.1485+2T>C Pathogenic ★★ same condition
CDHR1 c.1485+2T>G Pathogenic ★★ same condition
CDHR1 c.1554-2A>C Pathogenic/Likely pathogenic ★★ same condition
CDHR1 c.297+1G>T Pathogenic ★★ same condition
CDHR1 c.526-1G>A Likely pathogenic ★★ same condition
CDHR1 c.55+1G>A Likely pathogenic ★★ 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/cdhr1-p-glu680ter (accessed [today's date]).

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