Is CLIP3 p.Asp381Glu (c.1143C>G) pathogenic?

CLIP3 p.Asp381Glu (c.1143C>G) is classified Uncertain significance in CLIP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.6142); Ultra-rare (popmax 0.0187%, sas).

How common is CLIP3 p.Asp381Glu (c.1143C>G) in the general population?

CLIP3 p.Asp381Glu (c.1143C>G) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

What do computational predictors say about CLIP3 p.Asp381Glu (c.1143C>G)?

AlphaMissense predicts likely pathogenic (score 0.6142) — an in-silico prediction, not a clinical call.

CLIP3 p.Asp381Glu

c.1143C>G · rs371638018 · VCV2542766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6142 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6142	likely pathogenic
REVEL	0.248	benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 2,066 bp · p 0.0017 · regional, not allelic
Overall
CADD	22.6	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 0.0187% South Asian · 17/90,962 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00977%

Overall 0.00149% 24/1,613,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,351
Remaining individualsnot grpmax-eligible	0.00481%	20,811
East Asian	0.00445%	22,448
European (non-Finnish)	0.00017%	589,817

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: CLIP3
Protein: p.Asp381Glu
Coding: c.1143C>G
MANE Select: NM_015526
dbSNP: rs371638018
Type: single nucleotide variant
Location: chr19:36018938 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.93 · 1 PDB
Residue 381: the 'disordered' region

Full CLIP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP3 p.Ala137Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala148Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala214Thr Uncertain significance ★ ⚠ same type
CLIP3 p.Ala225Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala251Val Uncertain significance ★ ⚠ same type
CLIP3 p.Ala271Thr Uncertain significance ★ ⚠ same type
CLIP3 p.Ala30Ser Uncertain significance ★ ⚠ same type
CLIP3 p.Ala7Thr 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/clip3-p-asp381glu (accessed [today's date]).

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