Is NHS p.Pro1047= (c.3141C>T) pathogenic?

NHS p.Pro1047= (c.3141C>T) is classified Benign in NHS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-13). Ultra-rare (popmax 0.0355%, eas); Associated with Nance-Horan syndrome.

What condition is associated with NHS p.Pro1047= (c.3141C>T)?

NHS p.Pro1047= (c.3141C>T) is associated with Nance-Horan syndrome (ClinVar).

How common is NHS p.Pro1047= (c.3141C>T) in the general population?

NHS p.Pro1047= (c.3141C>T) is ultra-rare (popmax 0.0355%, eas) (gnomAD).

NHS p.Pro1047=

c.3141C>T · rs777688578 · VCV741801

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0355%, eas)

Conditions

Nance-Horan syndrome

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 -0.28	GERP -2.9, phastCons 0.44
Overall
CADD	5.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0355% East Asian · 12/33,793 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00355% 43/1,209,613 alleles · ultra-rare exomes 41/1,097,557 · genomes 2/112,056 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0355%	2,816
Remaining individualsnot grpmax-eligible	0.00841%	11,894
South Asian	0.00528%	18,939
European (non-Finnish)	0.00257%	38,901
Admixed American	0.00218%	45,799

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.Pro1047=
Coding: c.3141C>T
MANE Select: NM_001291867
dbSNP: rs777688578
Type: single nucleotide variant
Location: chrX:17727247 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 1047: the 'disordered' region

Full NHS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Nance-Horan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro1047 (accessed [today's date]).

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