Is NHS p.Val201Ala (c.602T>C) pathogenic?

NHS p.Val201Ala (c.602T>C) is classified Likely benign in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). Ultra-rare (popmax 0.0229%, mid); Associated with Inborn genetic diseases.

What condition is associated with NHS p.Val201Ala (c.602T>C)?

NHS p.Val201Ala (c.602T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NHS p.Val201Ala (c.602T>C) in the general population?

NHS p.Val201Ala (c.602T>C) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

NHS p.Val201Ala

c.602T>C · VCV3919549

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.178	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.76, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 357 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% Middle Eastern · 1/4,375 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00373%

Overall 0.000496% 6/1,210,154 alleles · ultra-rare exomes 4/1,098,216 · genomes 2/111,938 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,375
East Asian	0.0148%	6,746

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.Val201Ala
Coding: c.602T>C
MANE Select: NM_001291867
Type: single nucleotide variant
Location: chrX:17687778 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 201: the 'wave homology domain (whd)' 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.Val201Met Uncertain significance ★ same residue
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

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-val201ala (accessed [today's date]).

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