Is NPHP3 p.Ala1168= (c.3504A>G) pathogenic?

NPHP3 p.Ala1168= (c.3504A>G) is classified Conflicting classifications of pathogenicity in NPHP3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-05). Rare (popmax 0.115%, mid); Associated with renal-hepatic-pancreatic dysplasia 1.

What condition is associated with NPHP3 p.Ala1168= (c.3504A>G)?

NPHP3 p.Ala1168= (c.3504A>G) is associated with renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome, nephronophthisis 3 (ClinVar).

How common is NPHP3 p.Ala1168= (c.3504A>G) in the general population?

NPHP3 p.Ala1168= (c.3504A>G) is rare (popmax 0.115%, mid) (gnomAD).

NPHP3 p.Ala1168=

c.3504A>G · rs371505908 · VCV592218

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

renal-hepatic-pancreatic dysplasia 1

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.8	GERP -3.2
Overall
CADD	0.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0156% 252/1,614,094 alleles · rare exomes 224/1,461,740 · genomes 28/152,354 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
South Asian	0.0329%	3,036
Remaining individualsnot grpmax-eligible	0.0288%	3,472
European (non-Finnish)	0.0164%	6,114
Admixed American	0.005%	20,009
East Asian	0.00223%	44,884

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.Ala1168=
Coding: c.3504A>G
MANE Select: NM_153240
dbSNP: rs371505908
Type: single nucleotide variant
Location: chr3:132684620 (GRCh38)

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

Disease context

renal-hepatic-pancreatic dysplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: NPHP3-related Meckel-like syndrome nephronophthisis 3 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-ala1168 (accessed [today's date]).

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