Is ZYX p.Ala92Asp (c.275C>A) pathogenic?

ZYX p.Ala92Asp (c.275C>A) is classified Uncertain significance in ZYX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: ambiguous (0.3888); Absent from gnomAD v4.1.

How common is ZYX p.Ala92Asp (c.275C>A) in the general population?

ZYX p.Ala92Asp (c.275C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ZYX p.Ala92Asp (c.275C>A)?

AlphaMissense predicts ambiguous (score 0.3888) — an in-silico prediction, not a clinical call.

ZYX p.Ala92Asp

c.275C>A · VCV3823877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3888	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -3.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,107 bp · p 0.99 · regional, not allelic
Overall
CADD	20.5	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.Ala92Asp
Coding: c.275C>A
MANE Select: NM_003461
Type: single nucleotide variant
Location: chr7:143382314 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.57
Residue 92: the 'disordered' region

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

Similar variants

ZYX p.Ala92Gly Uncertain significance ★ ⚠ same residue
ZYX p.Ala92= Likely benign ★ same residue
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

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-ala92asp (accessed [today's date]).

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