Is NPHP3 p.Lys1063= (c.3189A>G) pathogenic?

NPHP3 p.Lys1063= (c.3189A>G) is classified Benign/Likely benign in NPHP3 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-20). Rare (popmax 0.422%, afr); Associated with NPHP3-related Meckel-like syndrome.

What condition is associated with NPHP3 p.Lys1063= (c.3189A>G)?

NPHP3 p.Lys1063= (c.3189A>G) is associated with NPHP3-related Meckel-like syndrome, kidney disorder, renal-hepatic-pancreatic dysplasia 1 (ClinVar).

How common is NPHP3 p.Lys1063= (c.3189A>G) in the general population?

NPHP3 p.Lys1063= (c.3189A>G) is rare (popmax 0.422%, afr) (gnomAD).

NPHP3 p.Lys1063=

c.3189A>G · rs112386774 · VCV262703

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.422%, afr)

Conditions

NPHP3-related Meckel-like syndrome

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 2.3	GERP 0.68, phastCons 1
Overall
CADD	7.302	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.422% African / African-American · 304/72,072 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.368%

Overall 0.0282% 413/1,463,642 alleles · rare exomes 232/1,311,386 · genomes 181/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.422%	237
Middle Eastern	0.104%	960
Remaining individualsnot grpmax-eligible	0.0958%	1,044
Admixed American	0.0655%	1,527
South Asian	0.00457%	21,877
European (non-Finnish)	0.000478%	209,104

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: NPHP3
Protein: p.Lys1063=
Coding: c.3189A>G
MANE Select: NM_153240
dbSNP: rs112386774
Type: single nucleotide variant
Location: chr3:132687163 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.59 · 1 PDB

Full NPHP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: kidney disorder renal-hepatic-pancreatic dysplasia 1 nephronophthisis 3 nephronophthisis

Similar variants

NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP3 c.3201+1G>T Likely pathogenic ★★ same condition
NPHP3 c.393+1G>C Likely pathogenic ★★ same condition
NPHP3 c.520-1G>T Pathogenic ★★ same condition
NPHP3 c.823+1G>T Likely pathogenic ★★ same condition
NPHP3 c.958-2A>G Pathogenic ★★ same condition
NPHP3 p.Arg1125Ter Pathogenic ★★ same condition
NPHP3 p.Arg1259Ter Pathogenic/Likely pathogenic ★★ 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/nphp3-p-lys1063 (accessed [today's date]).

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