Is NPHS2 p.Asp244= (c.732T>C) pathogenic?

NPHS2 p.Asp244= (c.732T>C) is classified Likely benign in NPHS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). Very rare (popmax 0.0011%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NPHS2 p.Asp244= (c.732T>C)?

NPHS2 p.Asp244= (c.732T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NPHS2 p.Asp244= (c.732T>C) in the general population?

NPHS2 p.Asp244= (c.732T>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

NPHS2 p.Asp244=

c.732T>C · rs779348692 · VCV1082872

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -0.63, phastCons 0.096
Overall
CADD	6.771	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,308 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,612,906 alleles · very rare exomes 12/1,460,682 · genomes 1/152,224 · 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: NPHS2
Protein: p.Asp244=
Coding: c.732T>C
MANE Select: NM_014625
dbSNP: rs779348692
Type: single nucleotide variant
Location: chr1:179557033 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.00
Residue 244: a UniProt-annotated variant site (in nphs2)

Full NPHS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHS2 p.Ala41Ser Uncertain significance ★★ ⚠ same condition
NPHS2 p.Ala61Thr Uncertain significance ★★ ⚠ same condition
NPHS2 p.Arg133Thr Uncertain significance ★★ ⚠ same condition
NPHS2 p.Arg50Trp Uncertain significance ★★ ⚠ same condition
NPHS2 p.Ala62Thr Uncertain significance ★ ⚠ same condition
NPHS2 p.Arg229Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
NPHS2 p.Arg38Leu Uncertain significance ★ ⚠ same condition
NPHS2 p.Asn199Ile Uncertain significance ★ ⚠ 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/nphs2-p-asp244 (accessed [today's date]).

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