Is DCST2 p.Ala341Val (c.1022C>T) pathogenic?

DCST2 p.Ala341Val (c.1022C>T) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: ambiguous (0.4028); Absent from gnomAD v4.1.

How common is DCST2 p.Ala341Val (c.1022C>T) in the general population?

DCST2 p.Ala341Val (c.1022C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCST2 p.Ala341Val (c.1022C>T)?

AlphaMissense predicts ambiguous (score 0.4028) — an in-silico prediction, not a clinical call.

DCST2 p.Ala341Val

c.1022C>T · VCV4009891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4028 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4028	ambiguous
REVEL	0.144	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	27.1	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.Ala341Val
Coding: c.1022C>T
MANE Select: NM_144622
Type: single nucleotide variant
Location: chr1:155030239 (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.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
DCST2 p.Ala748Thr 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-ala341val (accessed [today's date]).

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