Is NPC1 p.Asn701= (c.2103C>T) pathogenic?

NPC1 p.Asn701= (c.2103C>T) is classified Benign in NPC1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.96%, afr); Associated with Niemann-Pick disease, type C1.

What condition is associated with NPC1 p.Asn701= (c.2103C>T)?

NPC1 p.Asn701= (c.2103C>T) is associated with Niemann-Pick disease, type C1 (ClinVar).

How common is NPC1 p.Asn701= (c.2103C>T) in the general population?

NPC1 p.Asn701= (c.2103C>T) is low-frequency (popmax 3.96%, afr) (gnomAD).

How is Niemann-Pick disease type C inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NPC1 p.Asn701=

c.2103C>T · rs7227375 · VCV194159

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.96%, afr)

Conditions

Niemann-Pick disease, type C1

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 5.9	GERP 1.9, phastCons 1
Overall
CADD	8.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.96% African / African-American · 2,968/74,982 alleles

Filtering AF 3.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.79%

Overall 0.208% 3,351/1,614,106 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.96%	25
Admixed American	0.258%	387
Remaining individualsnot grpmax-eligible	0.242%	414
Middle Eastern	0.132%	758
South Asian	0.00549%	18,214
European (non-Finnish)	0.00534%	18,731
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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: NPC1
Protein: p.Asn701=
Coding: c.2103C>T
MANE Select: NM_000271
dbSNP: rs7227375
Type: single nucleotide variant
Location: chr18:23544371 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 20 PDB
Residue 701: the ssd domain; an α-helix

Full NPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Niemann-Pick disease, type C1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Niemann-Pick disease type C (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

NPC1 p.Asn701Ser Uncertain significance ★ same residue
NPC1 p.Asn701Lys Likely pathogenic ★ same residue
NPC1 c.1554-1009G>A Pathogenic ★★ same condition
NPC1 c.1757+1G>A Likely pathogenic ★★ same condition
NPC1 c.1947+5G>C Pathogenic/Likely pathogenic ★★ same condition
NPC1 c.2130+1G>A Pathogenic ★★ same condition
NPC1 c.2245+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPC1 c.2246-2A>G Pathogenic/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/npc1-p-asn701 (accessed [today's date]).

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