Is ZYX p.Pro121Ser (c.361C>T) pathogenic?

ZYX p.Pro121Ser (c.361C>T) is classified Uncertain significance in ZYX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.0895); Absent from gnomAD v4.1.

How common is ZYX p.Pro121Ser (c.361C>T) in the general population?

ZYX p.Pro121Ser (c.361C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ZYX p.Pro121Ser (c.361C>T)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

ZYX p.Pro121Ser

c.361C>T · rs768080249 · VCV3199722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -12.64	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -3.6
Regional constraint	o/e 1.00	unconstrained · MANE · 9,107 bp · p 0.99 · regional, not allelic
Overall
CADD	3.215	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ZYX
Protein: p.Pro121Ser
Coding: c.361C>T
MANE Select: NM_003461
dbSNP: rs768080249
Type: single nucleotide variant
Location: chr7:143382400 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.57
Residue 121: 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-pro121ser (accessed [today's date]).

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