Is NHS p.Pro206= (c.618G>A) pathogenic?

NHS p.Pro206= (c.618G>A) is classified Conflicting classifications of pathogenicity in NHS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-11). Ultra-rare (popmax 0.023%, mid); Associated with Inborn genetic diseases.

What condition is associated with NHS p.Pro206= (c.618G>A)?

NHS p.Pro206= (c.618G>A) is associated with Inborn genetic diseases, Nance-Horan syndrome (ClinVar).

How common is NHS p.Pro206= (c.618G>A) in the general population?

NHS p.Pro206= (c.618G>A) is ultra-rare (popmax 0.023%, mid) (gnomAD).

NHS p.Pro206=

c.618G>A · rs200952266 · VCV167353

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

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 -2.9	GERP -3.8
Overall
CADD	2.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,354 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.0105% 127/1,210,246 alleles · ultra-rare exomes 120/1,098,138 · genomes 7/112,108 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,354
European (non-Finnish)	0.0135%	7,398
East Asian	0.00593%	16,866
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,032
Remaining individualsnot grpmax-eligible	0.0021%	47,620
South Asian	0.00176%	56,819

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.Pro206=
Coding: c.618G>A
MANE Select: NM_001291867
dbSNP: rs200952266
Type: single nucleotide variant
Location: chrX:17687794 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 206: 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

Also linked: Nance-Horan syndrome

Similar variants

NHS p.Pro206Leu Uncertain significance ★ same residue
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

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-pro206 (accessed [today's date]).

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