Is NPHP1 p.Ala230Val (c.689C>T) pathogenic?

NPHP1 p.Ala230Val (c.689C>T) is classified Benign/Likely benign in NPHP1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0697); Low-frequency (popmax 3.72%, afr); Associated with kidney disorder.

What condition is associated with NPHP1 p.Ala230Val (c.689C>T)?

NPHP1 p.Ala230Val (c.689C>T) is associated with kidney disorder, nephronophthisis 1, Senior-Loken syndrome 1 (ClinVar).

How common is NPHP1 p.Ala230Val (c.689C>T) in the general population?

NPHP1 p.Ala230Val (c.689C>T) is low-frequency (popmax 3.72%, afr) (gnomAD).

What do computational predictors say about NPHP1 p.Ala230Val (c.689C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

NPHP1 p.Ala230Val

c.689C>T · rs113450177 · VCV235470

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.72%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

kidney disorder

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.13	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 0.18	GERP 0.2
Regional constraint	o/e 0.96	unconstrained · MANE · 81 kb · p 0.26 · regional, not allelic
Overall
CADD	4.273	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 3.72% African / African-American · 2,781/74,824 alleles

Filtering AF 3.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.55%

Overall 0.196% 3,169/1,613,368 alleles · low-frequency exomes 1,604/1,461,424 · genomes 1,565/151,944 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.72%	27
Admixed American	0.24%	417
Remaining individualsnot grpmax-eligible	0.226%	443
Middle Eastern	0.0495%	2,019
Finnishnot grpmax-eligible	0.00939%	10,654
European (non-Finnish)	0.00746%	13,406
South Asian	0.00659%	15,176

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: NPHP1
Protein: p.Ala230Val
Coding: c.689C>T
MANE Select: NM_001128178
dbSNP: rs113450177
Type: single nucleotide variant
Location: chr2:110165091 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB
Residue 230: the 'disordered' region

Full NPHP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 1 Senior-Loken syndrome 1 Joubert syndrome with renal defect nephronophthisis

Similar variants

NPHP1 p.Ala230= Likely benign ★★ same residue
NPHP1 c.1083+1G>A Likely pathogenic ★★ same condition
NPHP1 c.1270-1G>A Pathogenic ★★ same condition
NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.143+1G>C Likely pathogenic ★★ same condition
NPHP1 c.144-1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.1716+1G>T Pathogenic/Likely pathogenic ★★ same condition
NPHP1 c.329+1G>A 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/nphp1-p-ala230val (accessed [today's date]).

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