Is DIS3L2 p.Ser87Phe (c.260C>T) pathogenic?

DIS3L2 p.Ser87Phe (c.260C>T) is classified Uncertain significance in DIS3L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-10). AlphaMissense: ambiguous (0.4861); Absent from gnomAD v4.1; Associated with Perlman syndrome.

What condition is associated with DIS3L2 p.Ser87Phe (c.260C>T)?

DIS3L2 p.Ser87Phe (c.260C>T) is associated with Perlman syndrome (ClinVar).

How common is DIS3L2 p.Ser87Phe (c.260C>T) in the general population?

DIS3L2 p.Ser87Phe (c.260C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIS3L2 p.Ser87Phe (c.260C>T)?

AlphaMissense predicts ambiguous (score 0.4861) — an in-silico prediction, not a clinical call.

DIS3L2 p.Ser87Phe

c.260C>T · rs1694600552 · VCV1441190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4861 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Perlman syndrome

Computational evidence

Protein change
AlphaMissense	0.4861	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -12.23	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 319 kb · p 0.024 · regional, not allelic
Overall
CADD	25.5	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

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: DIS3L2
Protein: p.Ser87Phe
Coding: c.260C>T
MANE Select: NM_152383
dbSNP: rs1694600552
Type: single nucleotide variant
Location: chr2:232024326 (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.Ser87Thr Uncertain significance ★ ⚠ same residue
DIS3L2 p.Ser87= Likely benign ★ same residue
DIS3L2 p.Ser87fs Pathogenic ★ same residue
DIS3L2 c.1740-1G>C Likely pathogenic ★★ same condition
DIS3L2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Arg388Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Arg43Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Arg724Ter Pathogenic/Likely pathogenic ★★ 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-ser87phe (accessed [today's date]).

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