Is DCST2 p.Arg565Trp (c.1693C>T) pathogenic?

DCST2 p.Arg565Trp (c.1693C>T) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.166); Ultra-rare (popmax 0.0279%, sas).

How common is DCST2 p.Arg565Trp (c.1693C>T) in the general population?

DCST2 p.Arg565Trp (c.1693C>T) is ultra-rare (popmax 0.0279%, sas) (gnomAD).

What do computational predictors say about DCST2 p.Arg565Trp (c.1693C>T)?

AlphaMissense predicts likely benign (score 0.166) — an in-silico prediction, not a clinical call.

DCST2 p.Arg565Trp

c.1693C>T · rs756412235 · VCV2329663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0279%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.166	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -12.43	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP -0.016, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.0279% South Asian · 25/89,460 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.00286% 46/1,608,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0279%	3,578
Remaining individualsnot grpmax-eligible	0.00321%	31,148
European (non-Finnish)	0.00153%	65,410
African / African-American	0.00134%	74,724

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: DCST2
Protein: p.Arg565Trp
Coding: c.1693C>T
MANE Select: NM_144622
dbSNP: rs756412235
Type: single nucleotide variant
Location: chr1:155024521 (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.Arg565Gln Uncertain significance ★ ⚠ same residue
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

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-arg565trp (accessed [today's date]).

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