Is NDP p.Phe81Ser (c.242T>C) pathogenic?

NDP p.Phe81Ser (c.242T>C) is classified Likely pathogenic in NDP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-28). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1; Associated with Norrie disease.

What condition is associated with NDP p.Phe81Ser (c.242T>C)?

NDP p.Phe81Ser (c.242T>C) is associated with Norrie disease (ClinVar).

How common is NDP p.Phe81Ser (c.242T>C) in the general population?

NDP p.Phe81Ser (c.242T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NDP p.Phe81Ser (c.242T>C)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

NDP p.Phe81Ser

c.242T>C · rs2147204801 · VCV1339550

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Norrie disease

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic ✓ concordant with ClinVar · top 4% in NDP
REVEL	0.696	pathogenic-leaning
SaProt	LLR -6.58	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 0.74	unconstrained · MANE · 8,843 bp · p 0.0055 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NDP
Protein: p.Phe81Ser
Coding: c.242T>C
MANE Select: NM_000266
dbSNP: rs2147204801
Type: single nucleotide variant
Location: chrX:43949959 (GRCh38)
Structure: AlphaFold pLDDT 83.92 · 12 PDB
Residue 81: the ctck domain; a β-strand

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

Disease context

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

Similar variants

NDP p.Phe81Leu Uncertain significance ★ ⚠ same residue
NDP p.Arg121Trp Pathogenic/Likely pathogenic ★★ same condition
NDP p.Arg37Ter Pathogenic/Likely pathogenic ★★ same condition
NDP p.Arg74Cys Pathogenic ★★ same condition
NDP p.Cys128Ter Pathogenic ★★ same condition
NDP p.His42Arg Pathogenic ★★ ⚠ same condition
NDP p.Leu52Ter Pathogenic/Likely pathogenic ★★ same condition
NDP p.Leu61Phe 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/ndp-p-phe81ser (accessed [today's date]).

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