Is NSDHL p.Phe102= (c.306C>T) pathogenic?

NSDHL p.Phe102= (c.306C>T) is classified Benign/Likely benign in NSDHL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-15). Rare (popmax 0.299%, mid); Associated with connective tissue disorder.

What condition is associated with NSDHL p.Phe102= (c.306C>T)?

NSDHL p.Phe102= (c.306C>T) is associated with connective tissue disorder, CK syndrome, CHILD syndrome (ClinVar).

How common is NSDHL p.Phe102= (c.306C>T) in the general population?

NSDHL p.Phe102= (c.306C>T) is rare (popmax 0.299%, mid) (gnomAD).

NSDHL p.Phe102=

c.306C>T · rs141089248 · VCV707162

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.299%, mid)

Conditions

connective tissue disorder

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 1.7	GERP 0.66, phastCons 1
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.299% Middle Eastern · 13/4,343 alleles

Filtering AF 0.177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.152%

Overall 0.106% 1,281/1,205,777 alleles · rare exomes 1,124/1,093,843 · genomes 157/111,934 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.37%	42
Middle Easterngrpmax	0.299%	334
Remaining individualsnot grpmax-eligible	0.2%	499
Admixed American	0.197%	508
European (non-Finnish)	0.0617%	1,621
South Asian	0.0106%	9,450
African / African-American	0.0105%	9,522

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe102=
Coding: c.306C>T
MANE Select: NM_015922
dbSNP: rs141089248
Type: single nucleotide variant
Location: chrX:152858808 (GRCh38)
Structure: AlphaFold pLDDT 88.65 · 2 PDB
Residue 102: a β-strand

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: CK syndrome CHILD syndrome

Similar variants

NSDHL p.Ala346Gly Uncertain significance ★★ ⚠ same condition
NSDHL p.Arg15Trp Uncertain significance ★★ ⚠ same condition
NSDHL p.Arg88Gln Uncertain significance ★★ ⚠ same condition
NSDHL p.Asn187Ser Uncertain significance ★★ ⚠ same condition
NSDHL p.Ile177Val Uncertain significance ★★ ⚠ same condition
NSDHL p.Leu352Val Uncertain significance ★★ ⚠ same condition
NSDHL p.Lys344Arg Uncertain significance ★★ ⚠ same condition
NSDHL p.Lys373Arg 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/nsdhl-p-phe102 (accessed [today's date]).

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