Is NPHP3 p.Ala1184Val (c.3551C>T) pathogenic?

NPHP3 p.Ala1184Val (c.3551C>T) is classified Uncertain significance in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-13). AlphaMissense: likely pathogenic (0.942); Very rare (popmax 6.2e-05%); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Ala1184Val (c.3551C>T)?

NPHP3 p.Ala1184Val (c.3551C>T) is associated with nephronophthisis (ClinVar).

How common is NPHP3 p.Ala1184Val (c.3551C>T) in the general population?

NPHP3 p.Ala1184Val (c.3551C>T) is very rare (popmax 6.2e-05%) (gnomAD).

How is Nephronophthisis inherited?

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

What do computational predictors say about NPHP3 p.Ala1184Val (c.3551C>T)?

AlphaMissense predicts likely pathogenic (score 0.942) — an in-silico prediction, not a clinical call.

NPHP3 p.Ala1184Val

c.3551C>T · rs2530380170 · VCV2913173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis

Computational evidence

Protein change
AlphaMissense	0.942	likely pathogenic · top 7% in NPHP3
REVEL	0.755	pathogenic-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0019 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,952 alleles · very rare exomes 1/1,461,684 · genomes 0/152,268 · 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.Ala1184Val
Coding: c.3551C>T
MANE Select: NM_153240
dbSNP: rs2530380170
Type: single nucleotide variant
Location: chr3:132684573 (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

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

For Nephronophthisis (Orphanet):

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

Similar variants

NPHP3 p.Ala1184Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
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.958-2A>G Pathogenic ★★ same condition
NPHP3 p.Arg1125Ter Pathogenic ★★ same condition
NPHP3 p.Arg1259Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP3 p.Arg142Ter 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-ala1184val (accessed [today's date]).

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