Is NPHP3 p.Ala51Val (c.152C>T) pathogenic?

NPHP3 p.Ala51Val (c.152C>T) is classified Conflicting classifications of pathogenicity in NPHP3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.119); Ultra-rare (popmax 0.0774%, afr); Associated with nephronophthisis.

What condition is associated with NPHP3 p.Ala51Val (c.152C>T)?

NPHP3 p.Ala51Val (c.152C>T) is associated with nephronophthisis, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

How common is NPHP3 p.Ala51Val (c.152C>T) in the general population?

NPHP3 p.Ala51Val (c.152C>T) is ultra-rare (popmax 0.0774%, afr) (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.Ala51Val (c.152C>T)?

AlphaMissense predicts likely benign (score 0.119) — an in-silico prediction, not a clinical call.

NPHP3 p.Ala51Val

c.152C>T · rs577583077 · VCV843396

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.119 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0774%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis

⚠ 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	0.119	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP 0.38, phastCons 0.9
Regional constraint	o/e 1.01	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	11.68	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 0.0774% African / African-American · 54/69,780 alleles

Filtering AF 0.0609% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.055%

Overall 0.00781% 118/1,510,812 alleles · ultra-rare exomes 72/1,358,744 · genomes 46/152,068 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0774%	1,292
East Asian	0.019%	5,269
Remaining individualsnot grpmax-eligible	0.0137%	7,312
Admixed American	0.0128%	7,812
South Asian	0.00496%	20,157
European (non-Finnish)	0.00334%	29,966
Finnishnot grpmax-eligible	0.00216%	46,386

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.Ala51Val
Coding: c.152C>T
MANE Select: NM_153240
dbSNP: rs577583077
Type: single nucleotide variant
Location: chr3:132722204 (GRCh38)

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

Also linked: renal-hepatic-pancreatic dysplasia 1 NPHP3-related Meckel-like syndrome nephronophthisis 3

For Nephronophthisis (Orphanet):

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

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-ala51val (accessed [today's date]).

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