Is DCST2 p.Val57Ala (c.170T>C) pathogenic?

DCST2 p.Val57Ala (c.170T>C) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). AlphaMissense: likely benign (0.0777); Very rare (popmax 0.00017%, nfe).

How common is DCST2 p.Val57Ala (c.170T>C) in the general population?

DCST2 p.Val57Ala (c.170T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DCST2 p.Val57Ala (c.170T>C)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

DCST2 p.Val57Ala

c.170T>C · rs1213725840 · VCV2521366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -5.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.1	GERP 0.96, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	18.83	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 0.00017% European (non-Finnish) · 2/1,179,904 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,964 alleles · very rare exomes 2/1,461,682 · genomes 0/152,282 · joint denominator

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.Val57Ala
Coding: c.170T>C
MANE Select: NM_144622
dbSNP: rs1213725840
Type: single nucleotide variant
Location: chr1:155033532 (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-val57ala (accessed [today's date]).

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