Is DCST2 p.Ile513Val (c.1537A>G) pathogenic?

DCST2 p.Ile513Val (c.1537A>G) is classified Likely benign in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0593); Absent from gnomAD v4.1.

How common is DCST2 p.Ile513Val (c.1537A>G) in the general population?

DCST2 p.Ile513Val (c.1537A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCST2 p.Ile513Val (c.1537A>G)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

DCST2 p.Ile513Val

c.1537A>G · VCV4238235

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.2	GERP 0.24
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	11.03	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: DCST2
Protein: p.Ile513Val
Coding: c.1537A>G
MANE Select: NM_144622
Type: single nucleotide variant
Location: chr1:155026376 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.49

Full DCST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCST2 p.Ala135Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala141Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala20Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala341Val Uncertain significance ★ ⚠ same type
DCST2 p.Ala39Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala597Asp Uncertain significance ★ ⚠ same type
DCST2 p.Ala668Val Uncertain significance ★ ⚠ same type
DCST2 p.Ala670Val 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/dcst2-p-ile513val (accessed [today's date]).

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