Is NHS p.Ala103= (c.309G>T) pathogenic?

NHS p.Ala103= (c.309G>T) is classified Likely benign in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). Very rare (popmax 0.000483%, nfe); Associated with Nance-Horan syndrome.

What condition is associated with NHS p.Ala103= (c.309G>T)?

NHS p.Ala103= (c.309G>T) is associated with Nance-Horan syndrome (ClinVar).

How common is NHS p.Ala103= (c.309G>T) in the general population?

NHS p.Ala103= (c.309G>T) is very rare (popmax 0.000483%, nfe) (gnomAD).

NHS p.Ala103=

c.309G>T · rs2064344909 · VCV2045065

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000483%, nfe)

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 3.5	GERP -0.97, phastCons 0.61
Overall
CADD	10.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000483% European (non-Finnish) · 4/827,796 alleles

Filtering AF 0.000113% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.6e-05%

Overall 0.00038% 4/1,053,832 alleles · very rare exomes 4/941,385 · genomes 0/112,447 · 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.Ala103=
Coding: c.309G>T
MANE Select: NM_001291867
dbSNP: rs2064344909
Type: single nucleotide variant
Location: chrX:17376066 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 103: 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

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-ala103 (accessed [today's date]).

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