Is DCBLD2 p.Trp575Cys (c.1725G>T) pathogenic?

DCBLD2 p.Trp575Cys (c.1725G>T) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely pathogenic (0.9129); Absent from gnomAD v4.1.

How common is DCBLD2 p.Trp575Cys (c.1725G>T) in the general population?

DCBLD2 p.Trp575Cys (c.1725G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCBLD2 p.Trp575Cys (c.1725G>T)?

AlphaMissense predicts likely pathogenic (score 0.9129) — an in-silico prediction, not a clinical call.

DCBLD2 p.Trp575Cys

c.1725G>T · VCV3838496

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9129 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9129	likely pathogenic · top 6% in DCBLD2
REVEL	0.358	indeterminate
SaProt	LLR -5.22	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.0054 · regional, not allelic
Overall
CADD	24.8	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: DCBLD2
Protein: p.Trp575Cys
Coding: c.1725G>T
MANE Select: NM_080927
Type: single nucleotide variant
Location: chr3:98800712 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13

Full DCBLD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCBLD2 p.Lys391= Benign ★★ same type
DCBLD2 p.Ala182Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala24Ser Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Glu Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala304Val Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala341Thr Uncertain significance ★ ⚠ same type
DCBLD2 p.Ala482Asp 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/dcbld2-p-trp575cys (accessed [today's date]).

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