Is NUS1 p.Phe207Ser (c.620T>C) pathogenic?

NUS1 p.Phe207Ser (c.620T>C) is classified Uncertain significance in NUS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely pathogenic (0.9245); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NUS1 p.Phe207Ser (c.620T>C)?

NUS1 p.Phe207Ser (c.620T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NUS1 p.Phe207Ser (c.620T>C) in the general population?

NUS1 p.Phe207Ser (c.620T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NUS1 p.Phe207Ser (c.620T>C)?

AlphaMissense predicts likely pathogenic (score 0.9245) — an in-silico prediction, not a clinical call.

NUS1 p.Phe207Ser

c.620T>C · VCV4538174

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9245 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9245	likely pathogenic · top 8% in NUS1
REVEL	0.553	indeterminate
SaProt	LLR -13.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 3.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 0.003 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: NUS1
Protein: p.Phe207Ser
Coding: c.620T>C
MANE Select: NM_138459
Type: single nucleotide variant
Location: chr6:117694109 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.01 · 9 PDB
Residue 207: a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; likely pathogenic); an α-helix

Full NUS1 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

NUS1 p.Phe207= Benign ★ same residue
NUS1 p.Ala187Val Uncertain significance ★★ ⚠ same condition
NUS1 p.Arg10Trp Uncertain significance ★★ ⚠ same condition
NUS1 p.Arg57Cys Uncertain significance ★★ ⚠ same condition
NUS1 p.Asn175Asp Uncertain significance ★★ ⚠ same condition
NUS1 p.Gln157Arg Uncertain significance ★★ ⚠ same condition
NUS1 p.Gln180Glu Uncertain significance ★★ ⚠ same condition
NUS1 p.Glu6Gln 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/nus1-p-phe207ser (accessed [today's date]).

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