Is NHP2 p.Val71= (c.213C>G) pathogenic?

NHP2 p.Val71= (c.213C>G) is classified Likely benign in NHP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Very rare (popmax 0.00133%, afr); Associated with dyskeratosis congenita.

What condition is associated with NHP2 p.Val71= (c.213C>G)?

NHP2 p.Val71= (c.213C>G) is associated with dyskeratosis congenita (ClinVar).

How common is NHP2 p.Val71= (c.213C>G) in the general population?

NHP2 p.Val71= (c.213C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

NHP2 p.Val71=

c.213C>G · rs575702154 · VCV703727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

dyskeratosis congenita

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 2.2	phastCons 1
Overall
CADD	11.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,052 alleles

Overall 6.2e-05% 1/1,614,170 alleles · very rare exomes 1/1,461,876 · genomes 0/152,294 · joint denominator

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: NHP2
Protein: p.Val71=
Coding: c.213C>G
MANE Select: NM_017838
dbSNP: rs575702154
Type: single nucleotide variant
Location: chr5:178153508 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.73 · 7 PDB
Residue 71: an α-helix

Full NHP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

NHP2 p.Ala17Val Uncertain significance ★★ ⚠ same condition
NHP2 p.Ala39Thr Uncertain significance ★★ ⚠ same condition
NHP2 p.Arg101Gly Uncertain significance ★★ ⚠ same condition
NHP2 p.Arg61Gln Uncertain significance ★★ ⚠ same condition
NHP2 p.Asp9Asn Uncertain significance ★★ ⚠ same condition
NHP2 p.Glu12Gln Uncertain significance ★★ ⚠ same condition
NHP2 p.Glu145Val Uncertain significance ★★ ⚠ same condition
NHP2 p.Gly63Arg 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/nhp2-p-val71 (accessed [today's date]).

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