Is NUS1 p.Phe114= (c.342C>T) pathogenic?

NUS1 p.Phe114= (c.342C>T) is classified Likely benign in NUS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). Very rare (popmax 0.00734%, eas); Associated with congenital disorder of glycosylation, type Iaa.

What condition is associated with NUS1 p.Phe114= (c.342C>T)?

NUS1 p.Phe114= (c.342C>T) is associated with congenital disorder of glycosylation, type Iaa (ClinVar).

How common is NUS1 p.Phe114= (c.342C>T) in the general population?

NUS1 p.Phe114= (c.342C>T) is very rare (popmax 0.00734%, eas) (gnomAD).

NUS1 p.Phe114=

c.342C>T · VCV3704544

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00734%, eas)

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 1.5	GERP 2.2, phastCons 1
Overall
CADD	10.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00734% East Asian · 3/40,896 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000258% 4/1,549,664 alleles · very rare exomes 3/1,397,458 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00734%	13,632
European (non-Finnish)	8.72e-05%	1,146,938

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.Phe114=
Coding: c.342C>T
MANE Select: NM_138459
Type: single nucleotide variant
Location: chr6:117676012 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.01 · 9 PDB
Residue 114: 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 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
NUS1 p.Arg217Ile 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-phe114 (accessed [today's date]).

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