Is DPYSL3 p.Ile596Val (c.1786A>G) pathogenic?

DPYSL3 p.Ile596Val (c.1786A>G) is classified Uncertain significance in DPYSL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.00223%, eas).

How common is DPYSL3 p.Ile596Val (c.1786A>G) in the general population?

DPYSL3 p.Ile596Val (c.1786A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DPYSL3 p.Ile596Val (c.1786A>G)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

DPYSL3 p.Ile596Val

c.1786A>G · VCV3842371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -6.27	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 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 116 kb · p 3.9e-09 · regional, not allelic
Overall
CADD	21.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I482V vs ClinVar I596V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,860 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
South Asian	0.0011%	91,058
European (non-Finnish)	0.000678%	147,487

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DPYSL3
Protein: p.Ile596Val
Coding: c.1786A>G
MANE Select: NM_001197294
Type: single nucleotide variant
Location: chr5:147397683 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 4 PDB

Full DPYSL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPYSL3 p.Ala147Val Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala174Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala210Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala530Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala630Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Arg475Trp Uncertain significance ★ same type
DPYSL3 p.Arg581His Uncertain significance ★ ⚠ same type
DPYSL3 p.Arg634Trp 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/dpysl3-p-ile596val (accessed [today's date]).

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