Is ANAPC4 p.Gly467Glu (c.1400G>A) pathogenic?

ANAPC4 p.Gly467Glu (c.1400G>A) is classified Uncertain significance in ANAPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely pathogenic (0.8878); Very rare (popmax 6.87e-05%).

How common is ANAPC4 p.Gly467Glu (c.1400G>A) in the general population?

ANAPC4 p.Gly467Glu (c.1400G>A) is very rare (popmax 6.87e-05%) (gnomAD).

What do computational predictors say about ANAPC4 p.Gly467Glu (c.1400G>A)?

AlphaMissense predicts likely pathogenic (score 0.8878) — an in-silico prediction, not a clinical call.

ANAPC4 p.Gly467Glu

c.1400G>A · rs1723301499 · VCV3117878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8878	likely pathogenic
REVEL	0.294	indeterminate
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 25 kb · p 6.6e-06 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 6.87e-05%

Overall 6.87e-05% 1/1,456,136 alleles · very rare

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: ANAPC4
Protein: p.Gly467Glu
Coding: c.1400G>A
MANE Select: NM_013367
dbSNP: rs1723301499
Type: single nucleotide variant
Location: chr4:25407222 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.03 · 21 PDB

Full ANAPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANAPC4 c.515+1G>A Uncertain significance ★ same type
ANAPC4 p.Ala389Ser Uncertain significance ★ ⚠ same type
ANAPC4 p.Ala626Thr Uncertain significance ★ ⚠ same type
ANAPC4 p.Ala781Ser Uncertain significance ★ ⚠ same type
ANAPC4 p.Ala790Thr Uncertain significance ★ ⚠ same type
ANAPC4 p.Ala81Val Uncertain significance ★ ⚠ same type
ANAPC4 p.Ala85Val Uncertain significance ★ ⚠ same type
ANAPC4 p.Arg250Gln 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/anapc4-p-gly467glu (accessed [today's date]).

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