Is NHS p.Pro21= (c.63C>A) pathogenic?

NHS p.Pro21= (c.63C>A) is classified Likely benign in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-18). No allele count reported in gnomAD v4.1 (AN 1,151,688); Associated with Inborn genetic diseases.

What condition is associated with NHS p.Pro21= (c.63C>A)?

NHS p.Pro21= (c.63C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NHS p.Pro21= (c.63C>A) in the general population?

NHS p.Pro21= (c.63C>A) is no allele count reported in gnomAD v4.1 (AN 1,151,688) (gnomAD).

NHS p.Pro21=

c.63C>A · rs1435156319 · VCV1753296

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,151,688)

Conditions

Inborn genetic diseases

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	GERP -1.8
Overall
CADD	7.825	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,151,688). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NHS
Protein: p.Pro21=
Coding: c.63C>A
MANE Select: NM_001291867
dbSNP: rs1435156319
Type: single nucleotide variant
Location: chrX:17375820 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 21: the 'wave homology domain (whd)' region; the 'disordered' region

Full NHS 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

NHS p.Arg162Cys Uncertain significance ★★ same condition
NHS p.Arg17Trp Uncertain significance ★★ same condition
NHS p.Arg204His Uncertain significance ★★ same condition
NHS p.Arg231Gln Uncertain significance ★★ same condition
NHS p.Arg698Trp Uncertain significance ★★ same condition
NHS p.Asp1284His Uncertain significance ★★ same condition
NHS p.Cys1373Tyr Uncertain significance ★★ same condition
NHS p.Glu101Ala 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/nhs-p-pro21 (accessed [today's date]).

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