Is CLIP4 p.Lys94Glu (c.280A>G) pathogenic?

CLIP4 p.Lys94Glu (c.280A>G) is classified Uncertain significance in CLIP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: ambiguous (0.3865); Very rare (popmax 0.00834%, amr).

How common is CLIP4 p.Lys94Glu (c.280A>G) in the general population?

CLIP4 p.Lys94Glu (c.280A>G) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CLIP4 p.Lys94Glu (c.280A>G)?

AlphaMissense predicts ambiguous (score 0.3865) — an in-silico prediction, not a clinical call.

CLIP4 p.Lys94Glu

c.280A>G · VCV4229956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Computational evidence

Protein change
AlphaMissense	0.3865	ambiguous
REVEL	0.295	indeterminate
SaProt	LLR -9.84	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.2	GERP -0.55, phastCons 1
Overall
CADD	26.9	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 0.00834% Admixed American · 5/59,986 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000342% 5/1,460,724 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: CLIP4
Protein: p.Lys94Glu
Coding: c.280A>G
MANE Select: NM_018961 · reported on NM_024692
Type: single nucleotide variant
Location: chr2:29132158 (GRCh38)
Structure: AlphaFold pLDDT 82.62 · 2 PDB

Full CLIP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP4 p.Lys94Asn Uncertain significance ★ ⚠ same residue
UBASH3A p.Ile463Phe Uncertain significance ★★ ⚠ same type
CLIP4 p.Thr555= Benign ★★ same type
UBASH3A c.1393+3A>C Benign ★★ same type
UBASH3A p.Gly601= Benign ★★ same type
UBASH3A p.Ile303= Benign ★★ same type
UBASH3A p.Ile658Val Benign ★★ same type
UBASH3A p.Phe304= Benign ★★ 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/clip4-p-lys94glu (accessed [today's date]).

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