Is DCST2 p.Arg93Gln (c.278G>A) pathogenic?

DCST2 p.Arg93Gln (c.278G>A) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely benign (0.0901); Ultra-rare (popmax 0.0735%, eas).

How common is DCST2 p.Arg93Gln (c.278G>A) in the general population?

DCST2 p.Arg93Gln (c.278G>A) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about DCST2 p.Arg93Gln (c.278G>A)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

DCST2 p.Arg93Gln

c.278G>A · VCV4009886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.53, phastCons 0.033
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	22.3	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 0.0735% East Asian · 33/44,882 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.047%

Overall 0.00447% 72/1,609,594 alleles · ultra-rare exomes 63/1,457,272 · genomes 9/152,322 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
European (non-Finnish)	0.00306%	32,731
African / African-American	0.00267%	37,407
Admixed American	0.0017%	58,798

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.Arg93Gln
Coding: c.278G>A
MANE Select: NM_144622
Type: single nucleotide variant
Location: chr1:155033255 (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.Arg93Trp 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-arg93gln (accessed [today's date]).

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