Is DIS3L2 p.Val195fs (c.580_581del) pathogenic?

DIS3L2 p.Val195fs (c.580581del) is classified Pathogenic in DIS3L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-26). Absent from gnomAD; Associated with Perlman syndrome.

What condition is associated with DIS3L2 p.Val195fs (c.580_581del)?

DIS3L2 p.Val195fs (c.580_581del) is associated with Perlman syndrome (ClinVar).

How common is DIS3L2 p.Val195fs (c.580_581del) in the general population?

DIS3L2 p.Val195fs (c.580_581del) is absent from gnomAD (gnomAD).

DIS3L2 p.Val195fs

c.580_581del · rs1696706093 · VCV953114

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Perlman syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.37	GERP -3.6, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DIS3L2
Protein: p.Val195fs
Coding: c.580_581del
MANE Select: NM_152383
dbSNP: rs1696706093
Type: Microsatellite
Location: chr2:232087697 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.26 · 4 PDB

Full DIS3L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Perlman syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIS3L2 p.Val195Ala Uncertain significance ★ ⚠ same residue
DIS3L2 p.Glu176dup Uncertain significance ★★ same condition
DIS3L2 p.Glu874del Uncertain significance ★★ same condition
DIS3L2 p.Glu874dup Uncertain significance ★★ same condition
DIS3L2 c.*11CCGCCTGCC[2] Benign/Likely benign ★★ same condition
DIS3L2 p.343DFS[1] Uncertain significance ★ same condition
DIS3L2 p.Glu310del Uncertain significance ★ same condition
DIS3L2 p.Glu584del 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/dis3l2-p-val195fs (accessed [today's date]).

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