Is NPHP3 p.Asn711Ser (c.2132A>G) pathogenic?

NPHP3 p.Asn711Ser (c.2132A>G) is classified Conflicting classifications of pathogenicity in NPHP3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0894); Rare (popmax 0.733%, eas); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with NPHP3 p.Asn711Ser (c.2132A>G)?

NPHP3 p.Asn711Ser (c.2132A>G) is associated with atypical hemolytic-uremic syndrome, renal-hepatic-pancreatic dysplasia 1, NPHP3-related Meckel-like syndrome (ClinVar).

How common is NPHP3 p.Asn711Ser (c.2132A>G) in the general population?

NPHP3 p.Asn711Ser (c.2132A>G) is rare (popmax 0.733%, eas) (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

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

What do computational predictors say about NPHP3 p.Asn711Ser (c.2132A>G)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

NPHP3 p.Asn711Ser

c.2132A>G · rs117872197 · VCV697112

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.733%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -4.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	21.1	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 0.733% East Asian · 329/44,886 alleles

Filtering AF 0.668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.642%

Overall 0.0224% 361/1,614,180 alleles · rare exomes 332/1,461,852 · genomes 29/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.733%	136
Remaining individualsnot grpmax-eligible	0.0208%	4,808
South Asian	0.0121%	8,281
European (non-Finnish)	0.000678%	147,502

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.Asn711Ser
Coding: c.2132A>G
MANE Select: NM_153240
dbSNP: rs117872197
Type: single nucleotide variant
Location: chr3:132696770 (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

atypical hemolytic-uremic syndrome — 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 nephronophthisis

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

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.520-1G>T Pathogenic ★★ same condition
NPHP3 c.823+1G>T 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

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-asn711ser (accessed [today's date]).

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