Is NSDHL p.Ser6= (c.18C>T) pathogenic?

NSDHL p.Ser6= (c.18C>T) is classified Likely benign in NSDHL (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-29). Very rare (popmax 0.00593%, eas).

How common is NSDHL p.Ser6= (c.18C>T) in the general population?

NSDHL p.Ser6= (c.18C>T) is very rare (popmax 0.00593%, eas) (gnomAD).

NSDHL p.Ser6=

c.18C>T · VCV4476483

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00593%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.036	GERP -2.6
Overall
CADD	0.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00593% East Asian · 2/33,739 alleles

Filtering AF 0.000982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000663% 8/1,206,280 alleles · very rare exomes 6/1,093,830 · genomes 2/112,450 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00593%	16,869
South Asian	0.00352%	28,385
Admixed American	0.00218%	45,859
European (non-Finnish)	0.000336%	297,272

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.Ser6=
Coding: c.18C>T
MANE Select: NM_015922
Type: single nucleotide variant
Location: chrX:152846342 (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.Ser6Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
NSDHL p.Ser6Asn Uncertain significance ★ ⚠ same residue
NSDHL p.Ser6Cys Uncertain significance ★ ⚠ same residue
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

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-ser6 (accessed [today's date]).

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