Is CLIP2 p.Arg768Trp (c.2302C>T) pathogenic?

CLIP2 p.Arg768Trp (c.2302C>T) is classified Benign in CLIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-03). AlphaMissense: likely benign (0.0959); Low-frequency (popmax 1.2%, afr).

How common is CLIP2 p.Arg768Trp (c.2302C>T) in the general population?

CLIP2 p.Arg768Trp (c.2302C>T) is low-frequency (popmax 1.2%, afr) (gnomAD).

What do computational predictors say about CLIP2 p.Arg768Trp (c.2302C>T)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

CLIP2 p.Arg768Trp

c.2302C>T · rs75721312 · VCV709126

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -10.47	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 0.028	GERP -4, phastCons 0.033
Regional constraint	o/e 0.87	unconstrained · MANE · 31 kb · p 0.00026 · regional, not allelic
Overall
CADD	21.6	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 1.2% African / African-American · 899/75,020 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0627% 1,011/1,613,058 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.2%	83
Middle Eastern	0.132%	758
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Admixed American	0.0668%	1,496
South Asian	0.00441%	22,685
Finnishnot grpmax-eligible	0.00313%	31,940
European (non-Finnish)	0.00127%	78,651

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: CLIP2
Protein: p.Arg768Trp
Coding: c.2302C>T
MANE Select: NM_003388
dbSNP: rs75721312
Type: single nucleotide variant
Location: chr7:74376703 (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.Arg768Gln Uncertain significance ★ ⚠ 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-arg768trp (accessed [today's date]).

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