Is NPHP3 p.Lys808Thr (c.2423A>C) pathogenic?

NPHP3 p.Lys808Thr (c.2423A>C) is classified Uncertain significance in NPHP3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-10). AlphaMissense: likely benign (0.1251); Very rare (popmax 0.00356%, nfe); Associated with NPHP3-related disorder.

What condition is associated with NPHP3 p.Lys808Thr (c.2423A>C)?

NPHP3 p.Lys808Thr (c.2423A>C) is associated with NPHP3-related disorder, nephronophthisis (ClinVar).

How common is NPHP3 p.Lys808Thr (c.2423A>C) in the general population?

NPHP3 p.Lys808Thr (c.2423A>C) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about NPHP3 p.Lys808Thr (c.2423A>C)?

AlphaMissense predicts likely benign (score 0.1251) — an in-silico prediction, not a clinical call.

NPHP3 p.Lys808Thr

c.2423A>C · rs763361711 · VCV942251

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1251 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NPHP3-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1251	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.18	GERP -2.5, phastCons 0.082
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0019 · regional, not allelic
Overall
CADD	13.95	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00356% European (non-Finnish) · 42/1,179,984 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.0026% 42/1,613,984 alleles · very rare exomes 36/1,461,766 · genomes 6/152,218 · 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: NPHP3
Protein: p.Lys808Thr
Coding: c.2423A>C
MANE Select: NM_153240
dbSNP: rs763361711
Type: single nucleotide variant
Location: chr3:132692706 (GRCh38)

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

Disease context

Also linked: nephronophthisis

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-lys808thr (accessed [today's date]).

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