Is NPHP3 p.Thr288= (c.864T>A) pathogenic?

NPHP3 p.Thr288= (c.864T>A) is classified Benign/Likely benign in NPHP3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-31). Common (popmax 6.03%, afr) — too common for a highly-penetrant pathogenic allele; Associated with kidney disorder.

What condition is associated with NPHP3 p.Thr288= (c.864T>A)?

NPHP3 p.Thr288= (c.864T>A) is associated with kidney disorder, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

NPHP3 p.Thr288=

Q: How common is NPHP3 p.Thr288= (c.864T>A) in the general population?

NPHP3 p.Thr288= (c.864T>A) is common (popmax 6.03%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.864T>A · rs147932449 · VCV197881

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 6.03%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

kidney disorder

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 -0.16	GERP -4, phastCons 0.006
Overall
CADD	4.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.03% African / African-American · 4,519/74,964 alleles

Filtering AF 5.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.82%

Overall 0.322% 5,188/1,611,492 alleles · common exomes 2,642/1,459,158 · genomes 2,546/152,334 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.03%	17
Remaining individualsnot grpmax-eligible	0.465%	215
Ashkenazi Jewishnot grpmax-eligible	0.352%	284
Admixed American	0.33%	303
Middle Eastern	0.198%	504
South Asian	0.00879%	11,377
European (non-Finnish)	0.00484%	20,662

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.Thr288=
Coding: c.864T>A
MANE Select: NM_153240
dbSNP: rs147932449
Type: single nucleotide variant
Location: chr3:132715178 (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

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal-hepatic-pancreatic dysplasia 1 NPHP3-related Meckel-like syndrome 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-thr288 (accessed [today's date]).

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