Is CNNM4 p.Val4fs (c.9_55del) pathogenic?

CNNM4 p.Val4fs (c.955del) is classified Pathogenic in CNNM4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-01-01). Very rare (popmax 0.000107%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with CNNM4 p.Val4fs (c.9_55del)?

CNNM4 p.Val4fs (c.9_55del) is associated with inherited retinal dystrophy (ClinVar).

How common is CNNM4 p.Val4fs (c.9_55del) in the general population?

CNNM4 p.Val4fs (c.9_55del) is very rare (popmax 0.000107%, nfe) (gnomAD).

CNNM4 p.Val4fs

c.9_55del · VCV3249983

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000107%, nfe)

Conditions

inherited retinal dystrophy

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 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.3	GERP -0.052, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000107% European (non-Finnish) · 1/932,402 alleles

Overall 0.0001% 1/997,316 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: CNNM4
Protein: p.Val4fs
Coding: c.9_55del
MANE Select: NM_020184
Type: Deletion
Location: chr2:96761002 (GRCh38)
Gene constraint: LOEUF 0.794 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.20 · 6 PDB

Full CNNM4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNNM4 p.Arg519Ter Pathogenic ★★ same condition
CNNM4 p.Gln564Ter Pathogenic ★★ same condition
CNNM4 p.Leu438fs Pathogenic/Likely pathogenic ★★ same condition
CNNM4 p.Tyr716Cys Likely pathogenic ★ same condition
CNNM4 p.Trp31Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
CNNM4 p.His294Tyr Likely pathogenic ⚠ same condition
CNNM4 p.Leu316Arg Likely pathogenic same condition
CNNM4 p.Cys151Arg 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/cnnm4-p-val4fs (accessed [today's date]).

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