Is ZNF423 p.Pro367= (c.1101T>C) pathogenic?

ZNF423 p.Pro367= (c.1101T>C) is classified Likely benign in ZNF423 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). Very rare (popmax 0.000339%, nfe); Associated with nephronophthisis 14.

What condition is associated with ZNF423 p.Pro367= (c.1101T>C)?

ZNF423 p.Pro367= (c.1101T>C) is associated with nephronophthisis 14 (ClinVar).

How common is ZNF423 p.Pro367= (c.1101T>C) in the general population?

ZNF423 p.Pro367= (c.1101T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

ZNF423 p.Pro367=

c.1101T>C · rs773496189 · VCV2893791

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 -2.3	GERP -5.1
Overall
CADD	2.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,972 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000558% 9/1,613,718 alleles · very rare exomes 8/1,461,552 · genomes 1/152,166 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,399
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)grpmax	0.000339%	294,993

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro367=
Coding: c.1101T>C
MANE Select: NM_001379286
dbSNP: rs773496189
Type: single nucleotide variant
Location: chr16:49638075 (GRCh38)
Gene constraint: LOEUF 0.196 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 1 PDB
Residue 367: the 'disordered' region

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 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
ZNF423 p.Ala25Thr 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-pro367 (accessed [today's date]).

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