Is CDHR1 p.Met1Val (c.1A>G) pathogenic?

CDHR1 p.Met1Val (c.1A>G) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2024-04-23). Very rare (popmax 0.00351%, nfe); Associated with CDHR1-related disorders.

What condition is associated with CDHR1 p.Met1Val (c.1A>G)?

CDHR1 p.Met1Val (c.1A>G) is associated with CDHR1-related disorders, cone-rod dystrophy 15, inherited retinal dystrophy (ClinVar).

How common is CDHR1 p.Met1Val (c.1A>G) in the general population?

CDHR1 p.Met1Val (c.1A>G) is very rare (popmax 0.00351%, nfe) (gnomAD).

CDHR1 p.Met1Val

c.1A>G · rs794726954 · VCV193474

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00351%, nfe)

Conditions

CDHR1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.225	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 3.5, phastCons 1
Overall
CADD	21.6	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 0.00351% European (non-Finnish) · 40/1,140,330 alleles

Filtering AF 0.00264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.0027% 41/1,519,498 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00351%	28,508
Remaining individualsnot grpmax-eligible	0.00169%	59,068

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.Met1Val
Coding: c.1A>G
MANE Select: NM_033100
dbSNP: rs794726954
Type: single nucleotide variant
Location: chr10:84194761 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79

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

Disease context

CDHR1-related disorders

Also linked: cone-rod dystrophy 15 inherited retinal dystrophy retinitis pigmentosa

Similar variants

CDHR1 p.Met1Leu Pathogenic same residue
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.525+1G>A 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-met1val (accessed [today's date]).

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