Is NSDHL p.Pro291= (c.873C>T) pathogenic?

NSDHL p.Pro291= (c.873C>T) is classified Likely benign in NSDHL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-29). Very rare (popmax 0.000112%, nfe).

How common is NSDHL p.Pro291= (c.873C>T) in the general population?

NSDHL p.Pro291= (c.873C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

NSDHL p.Pro291=

c.873C>T · VCV4953229

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 0.62	GERP -2.1, phastCons 1
Overall
CADD	7.604	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,076 alleles

Overall 8.27e-05% 1/1,209,207 alleles · very rare exomes 0/1,096,807 · genomes 1/112,400 · 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: NSDHL
Protein: p.Pro291=
Coding: c.873C>T
MANE Select: NM_015922
Type: single nucleotide variant
Location: chrX:152868867 (GRCh38)
Structure: AlphaFold pLDDT 88.65 · 2 PDB

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

Similar variants

NSDHL p.Ala290Val Uncertain significance ★★ ⚠ same type
NSDHL p.Ala346Gly Uncertain significance ★★ ⚠ same type
NSDHL p.Arg15Trp Uncertain significance ★★ ⚠ same type
NSDHL p.Arg220Gly Uncertain significance ★★ ⚠ same type
NSDHL p.Arg88Gln Uncertain significance ★★ ⚠ same type
NSDHL p.Asn187Ser Uncertain significance ★★ ⚠ same type
NSDHL p.Ile177Val Uncertain significance ★★ ⚠ same type
NSDHL p.Leu305Arg Uncertain significance ★★ ⚠ same type

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/nsdhl-p-pro291 (accessed [today's date]).

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