Is DCBLD2 p.Cys12Trp (c.36C>G) pathogenic?

DCBLD2 p.Cys12Trp (c.36C>G) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely benign (0.1533); Very rare (popmax 0.00244%, sas).

How common is DCBLD2 p.Cys12Trp (c.36C>G) in the general population?

DCBLD2 p.Cys12Trp (c.36C>G) is very rare (popmax 0.00244%, sas) (gnomAD).

What do computational predictors say about DCBLD2 p.Cys12Trp (c.36C>G)?

AlphaMissense predicts likely benign (score 0.1533) — an in-silico prediction, not a clinical call.

DCBLD2 p.Cys12Trp

c.36C>G · VCV3838495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1533	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -6.75	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 3.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 76 kb · p 0.018 · regional, not allelic
Overall
CADD	21.5	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 0.00244% South Asian · 2/81,818 alleles

Filtering AF 0.000406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000152%

Overall 0.000293% 4/1,366,368 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00244%	40,909
Remaining individualsnot grpmax-eligible	0.00169%	59,150
European (non-Finnish)	8.78e-05%	1,139,240

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: DCBLD2
Protein: p.Cys12Trp
Coding: c.36C>G
MANE Select: NM_080927
Type: single nucleotide variant
Location: chr3:98901291 (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.Cys12Phe Uncertain significance ★ ⚠ same residue
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

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-cys12trp (accessed [today's date]).

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