Is CLIP1 p.Arg780Trp (c.2338C>T) pathogenic?

CLIP1 p.Arg780Trp (c.2338C>T) is classified Conflicting classifications of pathogenicity in CLIP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-03-29). AlphaMissense: likely benign (0.0922); Rare (popmax 0.918%, eas).

How common is CLIP1 p.Arg780Trp (c.2338C>T) in the general population?

CLIP1 p.Arg780Trp (c.2338C>T) is rare (popmax 0.918%, eas) (gnomAD).

What do computational predictors say about CLIP1 p.Arg780Trp (c.2338C>T)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

CLIP1 p.Arg780Trp

c.2338C>T · rs3741447 · VCV434780

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.918%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -11.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.056, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 78 kb · p 3e-08 · regional, not allelic
Overall
CADD	24.2	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 0.918% East Asian · 412/44,882 alleles

Filtering AF 0.845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.816%

Overall 0.0332% 536/1,614,088 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.918%	109
Admixed American	0.0467%	2,143
South Asian	0.0461%	2,169
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.012%	8,335
European (non-Finnish)	0.00178%	56,191

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: CLIP1
Protein: p.Arg780Trp
Coding: c.2338C>T
MANE Select: NM_001247997
dbSNP: rs3741447
Type: single nucleotide variant
Location: chr12:122340866 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.16 · 11 PDB
Residue 780: a UniProt-annotated variant site (in)

Full CLIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP1 p.Arg780Gln Likely benign ★ same residue
CLIP1 p.Ala142Val Uncertain significance ★★ ⚠ same type
CLIP1 p.Arg342Cys Uncertain significance ★★ ⚠ same type
CLIP1 p.Gly1356Arg Uncertain significance ★★ ⚠ same type
CLIP1 p.Lys1267Arg Uncertain significance ★★ ⚠ same type
CLIP1 p.Ala1224Ser Likely benign ★★ same type
CLIP1 p.Ala301= Benign ★★ same type
CLIP1 p.Asn99= Benign/Likely 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/clip1-p-arg780trp (accessed [today's date]).

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