Is NHS p.Ala63= (c.189A>G) pathogenic?

NHS p.Ala63= (c.189A>G) is classified Likely benign in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-15). Very rare (popmax 0.000358%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NHS p.Ala63= (c.189A>G)?

NHS p.Ala63= (c.189A>G) is associated with Inborn genetic diseases (ClinVar).

How common is NHS p.Ala63= (c.189A>G) in the general population?

NHS p.Ala63= (c.189A>G) is very rare (popmax 0.000358%, nfe) (gnomAD).

NHS p.Ala63=

c.189A>G · rs1205606908 · VCV1782227

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000358%, nfe)

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 0.2	GERP -1.5, phastCons 0.009
Overall
CADD	7.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000358% European (non-Finnish) · 3/837,407 alleles

Filtering AF 9.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.6e-05%

Overall 0.000278% 3/1,080,611 alleles · very rare exomes 2/971,305 · genomes 1/109,306 · 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: NHS
Protein: p.Ala63=
Coding: c.189A>G
MANE Select: NM_001291867
dbSNP: rs1205606908
Type: single nucleotide variant
Location: chrX:17375946 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 63: 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-ala63 (accessed [today's date]).

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