Is DCST2 p.Arg632Cys (c.1894C>T) pathogenic?

DCST2 p.Arg632Cys (c.1894C>T) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.1244); Very rare (popmax 0.00518%, amr).

How common is DCST2 p.Arg632Cys (c.1894C>T) in the general population?

DCST2 p.Arg632Cys (c.1894C>T) is very rare (popmax 0.00518%, amr) (gnomAD).

What do computational predictors say about DCST2 p.Arg632Cys (c.1894C>T)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

DCST2 p.Arg632Cys

c.1894C>T · VCV4238219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00518%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 0.16, phastCons 0.98
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.00518% Admixed American · 3/57,872 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00194% 31/1,601,010 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00518%	19,291
African / African-American	0.00268%	37,356
South Asian	0.00225%	44,489
European (non-Finnish)	0.00204%	48,903

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.Arg632Cys
Coding: c.1894C>T
MANE Select: NM_144622
Type: single nucleotide variant
Location: chr1:155023434 (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

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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-arg632cys (accessed [today's date]).

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