Is CTLA4 p.Val84Ile (c.250G>A) pathogenic?

CTLA4 p.Val84Ile (c.250G>A) is classified Uncertain significance in CTLA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: likely benign (0.0818); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTLA4 p.Val84Ile (c.250G>A)?

CTLA4 p.Val84Ile (c.250G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CTLA4 p.Val84Ile (c.250G>A) in the general population?

CTLA4 p.Val84Ile (c.250G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTLA4 p.Val84Ile (c.250G>A)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

CTLA4 p.Val84Ile

c.250G>A · rs1422926559 · VCV3078630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.43, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 2,198 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	13.45	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: CTLA4
Protein: p.Val84Ile
Coding: c.250G>A
MANE Select: NM_005214
dbSNP: rs1422926559
Type: single nucleotide variant
Location: chr2:203870726 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.67 · 22 PDB
Residue 84: a disulfide bond; a β-strand; the ig-like v-type domain

Full CTLA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTLA4 p.Gly146Arg Pathogenic/Likely pathogenic ★★ same condition
CTLA4 p.Leu163Phe Uncertain significance ★★ ⚠ same condition
CTLA4 p.Met90Arg Uncertain significance ★★ ⚠ same condition
CTLA4 p.Ser55Asn Uncertain significance ★★ ⚠ same condition
CTLA4 p.Glu155Ala Uncertain significance ★ ⚠ same condition
CTLA4 p.Glu155Asp Uncertain significance ★ ⚠ same condition
CTLA4 p.Leu186Ser Uncertain significance ★ ⚠ same condition
CTLA4 p.Pro63Arg Uncertain significance ★ ⚠ same condition

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/ctla4-p-val84ile (accessed [today's date]).

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