Is CISH p.Val46= (c.138G>A) pathogenic?

CISH p.Val46= (c.138G>A) is classified Likely benign in CISH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-16). Absent from gnomAD v4.1; Associated with CISH-related disorder.

What condition is associated with CISH p.Val46= (c.138G>A)?

CISH p.Val46= (c.138G>A) is associated with CISH-related disorder (ClinVar).

How common is CISH p.Val46= (c.138G>A) in the general population?

CISH p.Val46= (c.138G>A) is absent from gnomAD v4.1 (gnomAD).

CISH p.Val46=

c.138G>A · rs2471650128 · VCV3029724

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CISH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -5.6
Overall
CADD	1.195	PHRED · no single calibrated threshold — expert panels disagree

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: CISH
Protein: p.Val46=
Coding: c.138G>A
MANE Select: NM_145071
dbSNP: rs2471650128
Type: single nucleotide variant
Location: chr3:50608476 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91

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

Disease context

CISH-related disorder

Similar variants

CISH c.*6C>T Likely benign same condition
CISH p.Arg78Gln Likely benign ★★ same type
CISH p.Leu223= Benign ★★ same type
CISH p.Ser173= Benign/Likely benign ★★ same type
CISH c.20+1222A>G Uncertain significance ★ same type
CISH c.20+1236G>A Uncertain significance ★ same type
CISH c.20+1246C>A Uncertain significance ★ same type
CISH p.Arg107His 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/cish-p-val46 (accessed [today's date]).

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