NPHP4 p.Thr962=
c.2886G>A · rs368320071 · VCV1108848
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0646%, eas)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.2 |
| Overall | ||
| CADD | 0.504 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0646%
East Asian · 29/44,880 alleles
Filtering AF
0.0461%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0399%
Overall
0.00516%
83/1,609,840 alleles · ultra-rare
exomes 75/1,457,520 · genomes 8/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0646% | 1,548 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.00769% | 13,009 |
| African / African-American | 0.00533% | 18,760 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
| Admixed American | 0.00333% | 30,008 |
| European (non-Finnish) | 0.00305% | 32,773 |
| Finnishnot grpmax-eligible | 0.00167% | 59,978 |
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
- NPHP4
- Protein
- p.Thr962=
- Coding
- c.2886G>A
- MANE Select
- NM_015102
- dbSNP
- rs368320071
- Type
- single nucleotide variant
- Location
- chr1:5875032 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
- Residue 962
- the 'sufficient for basal bodies localization' region
Similar variants
- NPHP4 p.Thr962Met Uncertain significance ★★ ⚠ same residue
- NPHP4 c.2304+1G>A Pathogenic ★★ same condition
- NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPHP4 c.2611+1G>C Pathogenic ★★ same condition
- NPHP4 c.3644+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPHP4 c.3644+1G>T Pathogenic/Likely pathogenic ★★ same condition
- NPHP4 c.518-2A>G Likely pathogenic ★★ same condition
- NPHP4 c.992+2T>C 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/nphp4-p-thr962 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown