Is NHS p.Pro71Ser (c.211C>T) pathogenic?

NHS p.Pro71Ser (c.211C>T) is classified Benign/Likely benign in NHS (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-31). Common (popmax 10%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with NHS p.Pro71Ser (c.211C>T)?

NHS p.Pro71Ser (c.211C>T) is associated with Inborn genetic diseases, Nance-Horan syndrome (ClinVar).

NHS p.Pro71Ser

Q: How common is NHS p.Pro71Ser (c.211C>T) in the general population?

NHS p.Pro71Ser (c.211C>T) is common (popmax 10%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.211C>T · rs398124605 · VCV96634

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 10%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.026	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.22, phastCons 0.11
Regional constraint	o/e 0.79	unconstrained · MANE · 357 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	6.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10% African / African-American · 5,139/51,273 alleles

Filtering AF 9.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.7%

Overall 0.557% 5,988/1,074,258 alleles · common exomes 2,788/962,991 · genomes 3,200/111,267 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10%	10
Remaining individualsnot grpmax-eligible	0.82%	122
Admixed American	0.747%	134
Middle Eastern	0.323%	309
South Asian	0.0391%	2,559
European (non-Finnish)	0.0306%	3,264
Finnishnot grpmax-eligible	0.00673%	14,869

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.Pro71Ser
Coding: c.211C>T
MANE Select: NM_001291867
dbSNP: rs398124605
Type: single nucleotide variant
Location: chrX:17375968 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 71: 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

Also linked: Nance-Horan syndrome

Similar variants

NHS p.Arg248Ter Pathogenic ★★ same condition
NHS p.Arg394Ter Pathogenic ★★ same condition
NHS p.Arg900Ter Pathogenic ★★ same condition
NHS p.Gln411Ter Pathogenic ★★ same condition
NHS p.Gln80Ter Pathogenic/Likely pathogenic ★★ same condition
NHS p.Ala564Val Uncertain significance ★★ same condition
NHS p.Ala745Val Uncertain significance ★★ same condition
NHS p.Arg162Cys 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-pro71ser (accessed [today's date]).

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