Is NPHP1 p.Thr267= (c.801G>A) pathogenic?

NPHP1 p.Thr267= (c.801G>A) is classified Conflicting classifications of pathogenicity in NPHP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0823%, nfe); Associated with nephronophthisis.

What condition is associated with NPHP1 p.Thr267= (c.801G>A)?

NPHP1 p.Thr267= (c.801G>A) is associated with nephronophthisis, nephronophthisis 1, Senior-Loken syndrome 1 (ClinVar).

How common is NPHP1 p.Thr267= (c.801G>A) in the general population?

NPHP1 p.Thr267= (c.801G>A) is ultra-rare (popmax 0.0823%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

NPHP1 p.Thr267=

c.801G>A · rs141763330 · VCV330734

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0823%, nfe)

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -15	GERP -3.4
Overall
CADD	0.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0823% European (non-Finnish) · 970/1,179,300 alleles

Filtering AF 0.0779% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.0653% 1,053/1,613,254 alleles · ultra-rare exomes 994/1,461,078 · genomes 59/152,176 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.112%	893
European (non-Finnish)grpmax	0.0823%	1,216
African / African-American	0.0107%	9,374
Finnishnot grpmax-eligible	0.00625%	15,998
East Asian	0.00223%	44,866

Remaining individuals 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: NPHP1
Protein: p.Thr267=
Coding: c.801G>A
MANE Select: NM_001128178
dbSNP: rs141763330
Type: single nucleotide variant
Location: chr2:110163106 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB

Full NPHP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: nephronophthisis 1 Senior-Loken syndrome 1 Joubert syndrome with renal defect inherited retinal dystrophy

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP1 p.Thr267Met Likely benign ★★ same residue
NPHP1 c.1083+1G>A Likely pathogenic ★★ same condition
NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.143+1G>C Likely pathogenic ★★ same condition
NPHP1 c.144-1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.1716+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.329+1G>A 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/nphp1-p-thr267 (accessed [today's date]).

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