Is ZYX p.Pro64= (c.192C>T) pathogenic?

ZYX p.Pro64= (c.192C>T) is classified Likely benign in ZYX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). Rare (popmax 0.158%, nfe).

How common is ZYX p.Pro64= (c.192C>T) in the general population?

ZYX p.Pro64= (c.192C>T) is rare (popmax 0.158%, nfe) (gnomAD).

ZYX p.Pro64=

c.192C>T · rs371579974 · VCV2658116

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.158%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.53	GERP 2.6, phastCons 0.99
Overall
CADD	12.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.158% European (non-Finnish) · 1,831/1,161,858 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.125% 1,968/1,577,228 alleles · rare exomes 1,850/1,424,908 · genomes 118/152,320 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.158%	635
Middle Eastern	0.118%	846
Remaining individualsnot grpmax-eligible	0.107%	935
Admixed American	0.0695%	1,438
South Asian	0.0126%	7,951
African / African-American	0.0123%	8,144
Finnishnot grpmax-eligible	0.00999%	10,008

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: ZYX
Protein: p.Pro64=
Coding: c.192C>T
MANE Select: NM_003461
dbSNP: rs371579974
Type: single nucleotide variant
Location: chr7:143381763 (GRCh38)

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

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/zyx-p-pro64 (accessed [today's date]).

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