Is NUS1 p.Phe207= (c.621T>C) pathogenic?

NUS1 p.Phe207= (c.621T>C) is classified Benign in NUS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). Very rare (popmax 8.48e-05%, nfe); Associated with congenital disorder of glycosylation, type Iaa.

What condition is associated with NUS1 p.Phe207= (c.621T>C)?

NUS1 p.Phe207= (c.621T>C) is associated with congenital disorder of glycosylation, type Iaa (ClinVar).

How common is NUS1 p.Phe207= (c.621T>C) in the general population?

NUS1 p.Phe207= (c.621T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

NUS1 p.Phe207=

c.621T>C · rs139972165 · VCV2197745

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

congenital disorder of glycosylation, type Iaa

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 0.65	GERP 1.4, phastCons 1
Overall
CADD	8.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,256 alleles

Overall 0.00391% 63/1,612,694 alleles · very rare exomes 54/1,460,536 · genomes 9/152,158 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.186%	538
Remaining individualsnot grpmax-eligible	0.0112%	8,915
European (non-Finnish)grpmax	8.48e-05%	1,179,256

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NUS1
Protein: p.Phe207=
Coding: c.621T>C
MANE Select: NM_138459
dbSNP: rs139972165
Type: single nucleotide variant
Location: chr6:117694110 (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

congenital disorder of glycosylation, type Iaa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NUS1 p.Phe207Ser Uncertain significance ★★ ⚠ same residue
NUS1 c.415+1G>A Pathogenic/Likely pathogenic ★★ same condition
NUS1 c.692-2A>G Likely pathogenic ★★ same condition
NUS1 p.Arg290Cys Pathogenic/Likely pathogenic ★★ same condition
NUS1 p.Leu240Ter Pathogenic/Likely pathogenic ★★ same condition
NUS1 p.Ala44Thr Uncertain significance ★★ ⚠ same condition
NUS1 p.Ala79Val Uncertain significance ★★ ⚠ same condition
NUS1 p.Arg10Trp 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-phe207 (accessed [today's date]).

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