Is NLGN4X p.Ile172= (c.516C>T) pathogenic?

NLGN4X p.Ile172= (c.516C>T) is classified Conflicting classifications of pathogenicity in NLGN4X (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2020-03-11). Rare (popmax 0.213%, eas); Associated with Inborn genetic diseases.

What condition is associated with NLGN4X p.Ile172= (c.516C>T)?

NLGN4X p.Ile172= (c.516C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NLGN4X p.Ile172= (c.516C>T) in the general population?

NLGN4X p.Ile172= (c.516C>T) is rare (popmax 0.213%, eas) (gnomAD).

NLGN4X p.Ile172=

c.516C>T · rs182247389 · VCV166890

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.213%, eas)

Conditions

Inborn genetic diseases

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 0.86	GERP -1.2, phastCons 1
Overall
CADD	1.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% East Asian · 72/33,732 alleles

Filtering AF 0.174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.00612% 74/1,208,675 alleles · rare exomes 71/1,097,545 · genomes 3/111,130 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.213%	469
Middle Eastern	0.023%	4,349
Remaining individualsnot grpmax-eligible	0.0021%	47,586

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: NLGN4X
Protein: p.Ile172=
Coding: c.516C>T
MANE Select: NM_181332
dbSNP: rs182247389
Type: single nucleotide variant
Location: chrX:6029389 (GRCh38)
Structure: AlphaFold pLDDT 78.99 · 3 PDB
Residue 172: a β-strand

Full NLGN4X gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NLGN4X p.Ala283Ser Uncertain significance ★★ ⚠ same condition
NLGN4X p.Arg298Gln Uncertain significance ★★ ⚠ same condition
NLGN4X p.Asp157Gly Uncertain significance ★★ ⚠ same condition
NLGN4X p.Glu674Lys Uncertain significance ★★ ⚠ same condition
NLGN4X p.Gly382Ser Uncertain significance ★★ ⚠ same condition
NLGN4X p.Leu762Val Uncertain significance ★★ ⚠ same condition
NLGN4X p.Met20Thr Uncertain significance ★★ ⚠ same condition
NLGN4X p.Met789Leu 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/nlgn4x-p-ile172 (accessed [today's date]).

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