Is CNNM4 p.Phe93fs (c.279del) pathogenic?

CNNM4 p.Phe93fs (c.279del) is classified Pathogenic in CNNM4 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-25). Very rare (popmax 0.000932%, nfe).

How common is CNNM4 p.Phe93fs (c.279del) in the general population?

CNNM4 p.Phe93fs (c.279del) is very rare (popmax 0.000932%, nfe) (gnomAD).

CNNM4 p.Phe93fs

c.279del · rs1447882843 · VCV1069696

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

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 7.8	GERP 1.4, phastCons 1
Overall
CADD	23.8	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 0.000932% European (non-Finnish) · 11/1,180,008 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,862 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.Phe93fs
Coding: c.279del
MANE Select: NM_020184
dbSNP: rs1447882843
Type: Deletion
Location: chr2:96761278 (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

Similar variants

CNNM4 c.1402+22del Benign/Likely benign ★★ same type
CNNM4 p.Gly735_Thr737del Likely benign ★★ same type
CNNM4 p.Asn250fs Pathogenic ★ same type
CNNM4 p.Asp114fs Pathogenic ★ same type
CNNM4 p.Asp157fs Pathogenic ★ same type
CNNM4 p.Asp433fs Pathogenic ★ same type
CNNM4 p.Gly205_Leu206del Pathogenic ★ same type
CNNM4 p.Gly364fs Pathogenic ★ 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/cnnm4-p-phe93fs (accessed [today's date]).

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