Is CLIP2 p.Asp890Glu (c.2670C>A) pathogenic?

CLIP2 p.Asp890Glu (c.2670C>A) is classified Uncertain significance in CLIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely pathogenic (0.6966); Absent from gnomAD v4.1.

How common is CLIP2 p.Asp890Glu (c.2670C>A) in the general population?

CLIP2 p.Asp890Glu (c.2670C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLIP2 p.Asp890Glu (c.2670C>A)?

AlphaMissense predicts likely pathogenic (score 0.6966) — an in-silico prediction, not a clinical call.

CLIP2 p.Asp890Glu

c.2670C>A · VCV4229941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6966	likely pathogenic
REVEL	0.422	indeterminate
SaProt	LLR -6.35	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 -6.4	GERP -6.7
Regional constraint	o/e 0.87	unconstrained · MANE · 31 kb · p 0.00026 · regional, not allelic
Overall
CADD	9.999	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: CLIP2
Protein: p.Asp890Glu
Coding: c.2670C>A
MANE Select: NM_003388
Type: single nucleotide variant
Location: chr7:74389209 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 2 PDB

Full CLIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP2 p.Asp890= Benign ★ same residue
CLIP2 p.Arg12His Uncertain significance ★★ ⚠ same type
CLIP2 p.Ala123= Benign ★★ same type
CLIP2 p.Arg932= Benign ★★ same type
CLIP2 p.Asn205= Benign ★★ same type
CLIP2 p.Asn910= Benign/Likely benign ★★ same type
CLIP2 p.His159= Benign/Likely benign ★★ same type
CLIP2 p.Ile396= 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/clip2-p-asp890glu (accessed [today's date]).

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