Is ZNF423 p.Pro970= (c.2910C>G) pathogenic?

ZNF423 p.Pro970= (c.2910C>G) is classified Likely benign in ZNF423 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). Very rare (popmax 0.00133%, afr); Associated with nephronophthisis 14.

What condition is associated with ZNF423 p.Pro970= (c.2910C>G)?

ZNF423 p.Pro970= (c.2910C>G) is associated with nephronophthisis 14 (ClinVar).

How common is ZNF423 p.Pro970= (c.2910C>G) in the general population?

ZNF423 p.Pro970= (c.2910C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Nephronophthisis inherited?

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

ZNF423 p.Pro970=

c.2910C>G · rs1972697473 · VCV1577873

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

nephronophthisis 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -3.1, phastCons 1
Overall
CADD	8.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,066 alleles

Overall 6.2e-05% 1/1,612,932 alleles · very rare exomes 1/1,460,606 · genomes 0/152,326 · joint denominator

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: ZNF423
Protein: p.Pro970=
Coding: c.2910C>G
MANE Select: NM_001379286
dbSNP: rs1972697473
Type: single nucleotide variant
Location: chr16:49636266 (GRCh38)
Gene constraint: LOEUF 0.196 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 1 PDB
Residue 970: a β-strand

Full ZNF423 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

ZNF423 p.Pro970Thr Uncertain significance ★ ⚠ same residue
ZNF423 c.40+33052G>A Uncertain significance ★★ same condition
ZNF423 p.Ala1075Thr Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala1101Thr Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala1108Thr Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala1291Val Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala19Val Uncertain significance ★★ ⚠ same condition
ZNF423 p.Ala25Gly 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/znf423-p-pro970 (accessed [today's date]).

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