Is DIS3 p.Ile779Phe (c.2335A>T) pathogenic?

DIS3 p.Ile779Phe (c.2335A>T) is classified Likely pathogenic in DIS3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-31). AlphaMissense: likely pathogenic (0.991); Absent from gnomAD v4.1; Associated with plasma cell myeloma.

What condition is associated with DIS3 p.Ile779Phe (c.2335A>T)?

DIS3 p.Ile779Phe (c.2335A>T) is associated with plasma cell myeloma (ClinVar).

How common is DIS3 p.Ile779Phe (c.2335A>T) in the general population?

DIS3 p.Ile779Phe (c.2335A>T) is absent from gnomAD v4.1 (gnomAD).

How is Multiple myeloma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DIS3 p.Ile779Phe (c.2335A>T)?

AlphaMissense predicts likely pathogenic (score 0.991) — an in-silico prediction, not a clinical call.

DIS3 p.Ile779Phe

c.2335A>T · rs1593835248 · VCV800341

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

plasma cell myeloma

Computational evidence

Protein change
AlphaMissense	0.991	likely pathogenic ✓ concordant with ClinVar · top 8% in DIS3
REVEL	0.707	pathogenic-leaning
SaProt	LLR -13.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 18 kb · p 0.072 · regional, not allelic
Overall
CADD	28.9	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

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: DIS3
Protein: p.Ile779Phe
Coding: c.2335A>T
MANE Select: NM_014953
dbSNP: rs1593835248
Type: single nucleotide variant
Location: chr13:72761930 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.12 · 3 PDB
Residue 779: the rnb domain

Full DIS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

plasma cell myeloma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple myeloma (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

DIS3 p.Ala518Thr Uncertain significance ★★ ⚠ same type
DIS3 p.Ala401Val Benign ★★ ⚠ same type
DIS3 p.Ter959Gln Likely benign ★★ same type
PIBF1 p.Ile51Val Benign/Likely benign ★★ same type
PIBF1 p.Met73Thr Benign/Likely benign ★★ same type
DIS3 p.Arg638Ter Likely pathogenic ★ same type
DIS3 c.228+3G>A Uncertain significance ★ same type
DIS3 c.2511+1G>C 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/dis3-p-ile779phe (accessed [today's date]).

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