Is ZYX p.Val238= (c.714C>T) pathogenic?

ZYX p.Val238= (c.714C>T) is classified Likely benign in ZYX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Very rare (popmax 0.00203%, nfe).

How common is ZYX p.Val238= (c.714C>T) in the general population?

ZYX p.Val238= (c.714C>T) is very rare (popmax 0.00203%, nfe) (gnomAD).

ZYX p.Val238=

c.714C>T · rs1030140570 · VCV2658119

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

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 -0.25	GERP -0.74
Overall
CADD	1.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,920 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,880 alleles · very rare exomes 24/1,461,712 · genomes 2/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,163
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-American	0.00134%	74,902

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.Val238=
Coding: c.714C>T
MANE Select: NM_003461
dbSNP: rs1030140570
Type: single nucleotide variant
Location: chr7:143383013 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.57
Residue 238: the 'disordered' region

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

Similar variants

ZYX p.Ala400= Benign ★★ same type
ZYX p.Thr459= Benign ★★ same type
ZYX p.Thr480= Benign ★★ same type
ZYX p.Ala107Glu Uncertain significance ★ ⚠ same type
ZYX p.Ala216Gly Uncertain significance ★ ⚠ same type
ZYX p.Ala317Val Uncertain significance ★ ⚠ same type
ZYX p.Ala408Ser Uncertain significance ★ ⚠ same type
ZYX p.Ala416Val 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/zyx-p-val238 (accessed [today's date]).

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