Is CDHR1 p.His206fs (c.616del) pathogenic?

CDHR1 p.His206fs (c.616del) is classified Pathogenic in CDHR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-09). Very rare (popmax 0.0011%, sas); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.His206fs (c.616del)?

CDHR1 p.His206fs (c.616del) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.His206fs (c.616del) in the general population?

CDHR1 p.His206fs (c.616del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CDHR1 p.His206fs

c.616del · rs1183979115 · VCV931851

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

cone-rod dystrophy 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 0.95, phastCons 0.98
Overall
CADD	25.4	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 0.0011% South Asian · 1/91,072 alleles

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

Overall 0.000249% 4/1,607,038 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000254%	393,286

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.His206fs
Coding: c.616del
MANE Select: NM_033100
dbSNP: rs1183979115
Type: Deletion
Location: chr10:84201895 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 206: the cadherin 2 domain

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

Disease context

cone-rod dystrophy 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDHR1 p.Asp238fs Pathogenic/Likely pathogenic ★★ same condition
CDHR1 p.Asp696fs Pathogenic ★★ same condition
CDHR1 p.Cys4fs Likely pathogenic ★★ same condition
CDHR1 p.Gly113fs Pathogenic ★★ same condition
CDHR1 p.Gly488fs Pathogenic ★★ same condition
CDHR1 p.Gly502fs Pathogenic ★★ same condition
CDHR1 p.Ile841fs Pathogenic/Likely pathogenic ★★ same condition
CDHR1 c.1782+1del 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-his206fs (accessed [today's date]).

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