Is NPHP1 p.Gln282Lys (c.844C>A) pathogenic?

NPHP1 p.Gln282Lys (c.844C>A) is classified Uncertain significance in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.0959); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NPHP1 p.Gln282Lys (c.844C>A)?

NPHP1 p.Gln282Lys (c.844C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NPHP1 p.Gln282Lys (c.844C>A) in the general population?

NPHP1 p.Gln282Lys (c.844C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about NPHP1 p.Gln282Lys (c.844C>A)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

NPHP1 p.Gln282Lys

c.844C>A · VCV4122085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.4	GERP 0.85, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 81 kb · p 0.26 · regional, not allelic
Overall
CADD	17.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q337K vs ClinVar Q282K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,554 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,400 alleles · very rare exomes 1/1,460,272 · genomes 1/152,128 · joint denominator

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.Gln282Lys
Coding: c.844C>A
MANE Select: NM_001128178
Type: single nucleotide variant
Location: chr2:110163063 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHP1 p.Gln282Leu Uncertain significance ★★ ⚠ same residue
NPHP1 p.Gln282Ter Pathogenic ★ same residue
NPHP1 p.Gln282Arg Uncertain significance ★ ⚠ same residue
NPHP1 p.Gly287Arg Pathogenic ★★ same condition
NPHP1 c.771+136C>A Uncertain significance ★★ ⚠ same condition
NPHP1 c.771+26A>G Uncertain significance ★★ ⚠ same condition
NPHP1 c.771+38G>T Uncertain significance ★★ ⚠ same condition
NPHP1 p.Arg389His 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/nphp1-p-gln282lys (accessed [today's date]).

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