Is NPHP3 p.Gly204Ser (c.610G>A) pathogenic?

NPHP3 p.Gly204Ser (c.610G>A) is classified Uncertain significance in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: ambiguous (0.3851); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with NPHP3 p.Gly204Ser (c.610G>A)?

NPHP3 p.Gly204Ser (c.610G>A) is associated with Inborn genetic diseases (ClinVar).

How common is NPHP3 p.Gly204Ser (c.610G>A) in the general population?

NPHP3 p.Gly204Ser (c.610G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about NPHP3 p.Gly204Ser (c.610G>A)?

AlphaMissense predicts ambiguous (score 0.3851) — an in-silico prediction, not a clinical call.

NPHP3 p.Gly204Ser

c.610G>A · rs1940132720 · VCV2378984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3851	ambiguous
REVEL	0.689	pathogenic-leaning
SaProt	LLR -7.80	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	27.7	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 0.0011% South Asian · 1/91,078 alleles

Overall 0.000124% 2/1,613,968 alleles · very rare exomes 2/1,461,796 · genomes 0/152,172 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,179,947

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.Gly204Ser
Coding: c.610G>A
MANE Select: NM_153240
dbSNP: rs1940132720
Type: single nucleotide variant
Location: chr3:132719054 (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

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

Similar variants

NPHP3 p.Ala1203Val Uncertain significance ★★ ⚠ same condition
NPHP3 p.Arg605Cys Uncertain significance ★★ ⚠ same condition
NPHP3 p.Arg705His Uncertain significance ★★ ⚠ same condition
NPHP3 p.Arg756Trp Uncertain significance ★★ ⚠ same condition
NPHP3 p.Asn1097Ser Uncertain significance ★★ ⚠ same condition
NPHP3 p.Asn218Ser Uncertain significance ★★ ⚠ same condition
NPHP3 p.Asn776Ser Uncertain significance ★★ ⚠ same condition
NPHP3 p.Gly235Arg 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/nphp3-p-gly204ser (accessed [today's date]).

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