Is DCST1 p.Pro42Gln (c.125C>A) pathogenic?

DCST1 p.Pro42Gln (c.125C>A) is classified Uncertain significance in DCST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.0953); Ultra-rare (popmax 0.0549%, sas).

How common is DCST1 p.Pro42Gln (c.125C>A) in the general population?

DCST1 p.Pro42Gln (c.125C>A) is ultra-rare (popmax 0.0549%, sas) (gnomAD).

What do computational predictors say about DCST1 p.Pro42Gln (c.125C>A)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

DCST1 p.Pro42Gln

c.125C>A · rs544612246 · VCV2616355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP -0.99, phastCons 0.079
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.35 · regional, not allelic
Overall
CADD	16.96	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 0.0549% South Asian · 50/91,054 alleles

Filtering AF 0.0427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.00322% 52/1,613,662 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0549%	1,821
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Pro42Gln
Coding: c.125C>A
MANE Select: NM_152494
dbSNP: rs544612246
Type: single nucleotide variant
Location: chr1:155034498 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.35

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

Similar variants

DCST1 p.Ala199Val Benign ★★ same type
DCST1 p.Thr158Ile Benign ★★ ⚠ same type
DCST1 p.Tyr362= Benign/Likely benign ★★ same type
DCST1 p.Ala103Thr Uncertain significance ★ ⚠ same type
DCST1 p.Ala124Pro Uncertain significance ★ ⚠ same type
DCST1 p.Ala124Thr Uncertain significance ★ ⚠ same type
DCST1 p.Ala219Val Uncertain significance ★ ⚠ same type
DCST1 p.Ala391Ser 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/dcst1-p-pro42gln (accessed [today's date]).

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