Is DIS3L p.Val367Ile (c.1099G>A) pathogenic?

DIS3L p.Val367Ile (c.1099G>A) is classified Uncertain significance in DIS3L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.2646); Absent from gnomAD v4.1.

How common is DIS3L p.Val367Ile (c.1099G>A) in the general population?

DIS3L p.Val367Ile (c.1099G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIS3L p.Val367Ile (c.1099G>A)?

AlphaMissense predicts likely benign (score 0.2646) — an in-silico prediction, not a clinical call.

DIS3L p.Val367Ile

c.1099G>A · rs375710056 · VCV2336158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2646 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2646	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -7.99	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 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 40 kb · p 0.0011 · regional, not allelic
Overall
CADD	23.1	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: DIS3L
Protein: p.Val367Ile
Coding: c.1099G>A
MANE Select: NM_001143688
dbSNP: rs375710056
Type: single nucleotide variant
Location: chr15:66318553 (GRCh38)
Gene constraint: LOEUF 0.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28 · 4 PDB
Residue 367: the csd2 domain; a β-strand

Full DIS3L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIS3L p.Ala146Thr Uncertain significance ★ ⚠ same type
DIS3L p.Ala362Val Uncertain significance ★ ⚠ same type
DIS3L p.Ala593Val Uncertain significance ★ ⚠ same type
DIS3L p.Ala693Thr Uncertain significance ★ ⚠ same type
DIS3L p.Ala740Ser Uncertain significance ★ ⚠ same type
DIS3L p.Ala740Val Uncertain significance ★ ⚠ same type
DIS3L p.Arg1026His Uncertain significance ★ ⚠ same type
DIS3L p.Arg1026Pro 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/dis3l-p-val367ile (accessed [today's date]).

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