Is DCST1 p.Val359Leu (c.1075G>T) pathogenic?

DCST1 p.Val359Leu (c.1075G>T) is classified Uncertain significance in DCST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1395); Absent from gnomAD v4.1.

How common is DCST1 p.Val359Leu (c.1075G>T) in the general population?

DCST1 p.Val359Leu (c.1075G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCST1 p.Val359Leu (c.1075G>T)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

DCST1 p.Val359Leu

c.1075G>T · VCV4658802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.24	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.6	GERP -1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.35 · regional, not allelic
Overall
CADD	13.52	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: DCST1
Protein: p.Val359Leu
Coding: c.1075G>T
MANE Select: NM_152494
Type: single nucleotide variant
Location: chr1:155043412 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.35

Full DCST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCST1 p.Ala199Val Benign ★★ same type
DCST1 p.Thr158Ile Benign ★★ ⚠ same type
DCST1 p.Tyr362= Benign/Likely benign ★★ same type
DCST1 p.Ala103Thr Uncertain significance ★ ⚠ same type
DCST1 p.Ala124Pro Uncertain significance ★ ⚠ same type
DCST1 p.Ala124Thr Uncertain significance ★ ⚠ same type
DCST1 p.Ala219Val Uncertain significance ★ ⚠ same type
DCST1 p.Ala391Ser 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/dcst1-p-val359leu (accessed [today's date]).

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