Is CLIP2 p.Ala265Val (c.794C>T) pathogenic?

CLIP2 p.Ala265Val (c.794C>T) is classified Uncertain significance in CLIP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.9546); Ultra-rare (popmax 0.0178%, eas).

How common is CLIP2 p.Ala265Val (c.794C>T) in the general population?

CLIP2 p.Ala265Val (c.794C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CLIP2 p.Ala265Val (c.794C>T)?

AlphaMissense predicts likely pathogenic (score 0.9546) — an in-silico prediction, not a clinical call.

CLIP2 p.Ala265Val

c.794C>T · rs1463617123 · VCV3145844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9546 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9546	likely pathogenic
REVEL	0.636	indeterminate
SaProt	LLR -9.85	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 7.5	GERP 6.9, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 18 kb · p 3.2e-08 · regional, not allelic
Overall
CADD	29.5	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 0.0178% East Asian · 8/44,840 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00118% 19/1,611,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,605
Admixed American	0.00167%	59,906
South Asian	0.0011%	90,882
European (non-Finnish)	0.000764%	130,940

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.Ala265Val
Coding: c.794C>T
MANE Select: NM_003388
dbSNP: rs1463617123
Type: single nucleotide variant
Location: chr7:74353995 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.25 · 2 PDB
Residue 265: the cap-gly 2 domain

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

Similar variants

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
CLIP2 p.Leu169= 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-ala265val (accessed [today's date]).

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