Is NPHP3 p.Phe172Ser (c.515T>C) pathogenic?

NPHP3 p.Phe172Ser (c.515T>C) is classified Uncertain significance in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-05-03). AlphaMissense: likely pathogenic (0.9987); No allele count reported in gnomAD v4.1 (AN 1,556,008).

How common is NPHP3 p.Phe172Ser (c.515T>C) in the general population?

NPHP3 p.Phe172Ser (c.515T>C) is no allele count reported in gnomAD v4.1 (AN 1,556,008) (gnomAD).

What do computational predictors say about NPHP3 p.Phe172Ser (c.515T>C)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

NPHP3 p.Phe172Ser

c.515T>C · rs886043761 · VCV287923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,556,008)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic · top 1% in NPHP3
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -8.54	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	27.5	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

No allele count reported in gnomAD v4.1 (AN 1,556,008). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NPHP3
Protein: p.Phe172Ser
Coding: c.515T>C
MANE Select: NM_153240
dbSNP: rs886043761
Type: single nucleotide variant
Location: chr3:132719709 (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

Similar variants

NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same type
NPHP3 c.3201+1G>T Likely pathogenic ★★ same type
NPHP3 c.393+1G>C Likely pathogenic ★★ same type
NPHP3 c.520-1G>T Pathogenic ★★ same type
NPHP3 c.823+1G>T Likely pathogenic ★★ same type
NPHP3 c.958-2A>G Pathogenic ★★ same type
NPHP3 p.Arg1125Ter Pathogenic ★★ same type
NPHP3 p.Arg1259Ter Pathogenic/Likely pathogenic ★★ same type

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-phe172ser (accessed [today's date]).

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