Is NPHP1 p.Gln638Arg (c.1913A>G) pathogenic?

NPHP1 p.Gln638Arg (c.1913A>G) is classified Conflicting classifications of pathogenicity in NPHP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0797); Rare (popmax 0.31%, eas); Associated with Inborn genetic diseases.

What condition is associated with NPHP1 p.Gln638Arg (c.1913A>G)?

NPHP1 p.Gln638Arg (c.1913A>G) is associated with Inborn genetic diseases, nephronophthisis (ClinVar).

How common is NPHP1 p.Gln638Arg (c.1913A>G) in the general population?

NPHP1 p.Gln638Arg (c.1913A>G) is rare (popmax 0.31%, eas) (gnomAD).

What do computational predictors say about NPHP1 p.Gln638Arg (c.1913A>G)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

NPHP1 p.Gln638Arg

c.1913A>G · rs186950965 · VCV216417

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.31%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.48	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 0.78	GERP 1.9, phastCons 0.66
Regional constraint	o/e 0.96	unconstrained · MANE · 81 kb · p 0.26 · regional, not allelic
Overall
CADD	17.97	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q693R vs ClinVar Q638R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% East Asian · 139/44,880 alleles

Filtering AF 0.268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.0102% 164/1,614,146 alleles · rare exomes 134/1,461,868 · genomes 30/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.31%	323
Remaining individualsnot grpmax-eligible	0.0256%	3,907
South Asian	0.00769%	13,012
Admixed American	0.00333%	30,015

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.Gln638Arg
Coding: c.1913A>G
MANE Select: NM_001128178
dbSNP: rs186950965
Type: single nucleotide variant
Location: chr2:110123912 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB

Full NPHP1 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

Also linked: nephronophthisis

Similar variants

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
NPHP1 c.522+1G>A Likely pathogenic ★★ same condition
NPHP1 c.729-2A>G 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-gln638arg (accessed [today's date]).

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