Is NYX p.Ala172Val (c.515C>T) pathogenic?

NYX p.Ala172Val (c.515C>T) is classified Uncertain significance in NYX (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-12). AlphaMissense: likely benign (0.2235); Ultra-rare (popmax 0.0651%, eas); Associated with Inborn genetic diseases.

What condition is associated with NYX p.Ala172Val (c.515C>T)?

NYX p.Ala172Val (c.515C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NYX p.Ala172Val (c.515C>T) in the general population?

NYX p.Ala172Val (c.515C>T) is ultra-rare (popmax 0.0651%, eas) (gnomAD).

What do computational predictors say about NYX p.Ala172Val (c.515C>T)?

AlphaMissense predicts likely benign (score 0.2235) — an in-silico prediction, not a clinical call.

NYX p.Ala172Val

c.515C>T · rs754612225 · VCV3203624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2235 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0651%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2235	likely benign
REVEL	0.444	indeterminate
SaProt	—	withheld · numbering disagrees past residue 4 · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.84 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A177V vs ClinVar A172V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0651% East Asian · 15/23,024 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0324%

Overall 0.00177% 19/1,072,984 alleles · ultra-rare exomes 16/961,052 · genomes 3/111,932 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0651%	1,535
Admixed American	0.00365%	27,362
Remaining individualsnot grpmax-eligible	0.00244%	41,040
European (non-Finnish)	0.00024%	416,854

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: NYX
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_001378477
dbSNP: rs754612225
Type: single nucleotide variant
Location: chrX:41473983 (GRCh38)
Structure: AlphaFold pLDDT 82.68

Full NYX 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

NYX p.Ala113Val Uncertain significance ★★ same condition
NYX p.Ala151Thr Uncertain significance ★★ ⚠ same condition
NYX p.Ala265Thr Uncertain significance ★★ ⚠ same condition
NYX p.Ala267Val Uncertain significance ★★ ⚠ same condition
NYX p.Ala28Thr Uncertain significance ★★ ⚠ same condition
NYX p.Ala31Asp Uncertain significance ★★ ⚠ same condition
NYX p.Ala53Val Uncertain significance ★★ ⚠ same condition
NYX p.Arg119His 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/nyx-p-ala172val (accessed [today's date]).

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