Is DCST1 p.Pro623Leu (c.1868C>T) pathogenic?

DCST1 p.Pro623Leu (c.1868C>T) is classified Uncertain significance in DCST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0781); Rare (popmax 0.325%, eas).

How common is DCST1 p.Pro623Leu (c.1868C>T) in the general population?

DCST1 p.Pro623Leu (c.1868C>T) is rare (popmax 0.325%, eas) (gnomAD).

What do computational predictors say about DCST1 p.Pro623Leu (c.1868C>T)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

DCST1 p.Pro623Leu

c.1868C>T · VCV4238214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.325%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0781	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -4.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.37	GERP -2.9
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.35 · regional, not allelic
Overall
CADD	3.043	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 0.325% East Asian · 146/44,884 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.266%

Overall 0.0152% 246/1,613,470 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.325%	307
African / African-American	0.101%	987
Remaining individualsnot grpmax-eligible	0.0048%	20,822
Admixed American	0.00333%	29,985
European (non-Finnish)	0.00153%	65,543
South Asian	0.0011%	90,978

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: DCST1
Protein: p.Pro623Leu
Coding: c.1868C>T
Type: single nucleotide variant
Location: chr1:155048169 (GRCh38)

Full DCST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dcst1-p-pro623leu (accessed [today's date]).

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