Is ZNF423 p.Ala487= (c.1461C>T) pathogenic?

ZNF423 p.Ala487= (c.1461C>T) is classified Likely benign in ZNF423 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). Very rare (popmax 0.00958%, nfe); Associated with nephronophthisis 14.

What condition is associated with ZNF423 p.Ala487= (c.1461C>T)?

ZNF423 p.Ala487= (c.1461C>T) is associated with nephronophthisis 14 (ClinVar).

How common is ZNF423 p.Ala487= (c.1461C>T) in the general population?

ZNF423 p.Ala487= (c.1461C>T) is very rare (popmax 0.00958%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

ZNF423 p.Ala487=

c.1461C>T · rs763866990 · VCV774385

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00958%, nfe)

Conditions

nephronophthisis 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.4, phastCons 1
Overall
CADD	7.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00958% European (non-Finnish) · 113/1,180,052 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0076%

Overall 0.00725% 117/1,614,052 alleles · very rare exomes 115/1,461,824 · genomes 2/152,228 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00958%	10,443
Admixed American	0.00667%	15,003

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.Ala487=
Coding: c.1461C>T
MANE Select: NM_001379286
dbSNP: rs763866990
Type: single nucleotide variant
Location: chr16:49637715 (GRCh38)
Gene constraint: LOEUF 0.196 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 1 PDB

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.Ala487Thr 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-ala487 (accessed [today's date]).

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