Is DCBLD1 p.Pro63Arg (c.188C>G) pathogenic?

DCBLD1 p.Pro63Arg (c.188C>G) is classified Uncertain significance in DCBLD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: ambiguous (0.5411); Very rare (popmax 0.00659%, sas).

How common is DCBLD1 p.Pro63Arg (c.188C>G) in the general population?

DCBLD1 p.Pro63Arg (c.188C>G) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about DCBLD1 p.Pro63Arg (c.188C>G)?

AlphaMissense predicts ambiguous (score 0.5411) — an in-silico prediction, not a clinical call.

DCBLD1 p.Pro63Arg

c.188C>G · VCV4009669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Computational evidence

Protein change
AlphaMissense	0.5411	ambiguous
REVEL	0.609	indeterminate
SaProt	LLR -9.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 66 kb · p 0.29 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.00659% South Asian · 6/91,076 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000434% 7/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,179
African / African-American	0.00134%	74,870

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: DCBLD1
Protein: p.Pro63Arg
Coding: c.188C>G
MANE Select: NM_001366458
Type: single nucleotide variant
Location: chr6:117503842 (GRCh38)
Gene constraint: LOEUF 0.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.00
Residue 63: a disulfide bond; the cub domain

Full DCBLD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCBLD1 p.Pro63His Uncertain significance ★ ⚠ same residue
DCBLD1 p.Asp151Asn Uncertain significance ★★ ⚠ same type
DCBLD1 p.Ala15Ser Uncertain significance ★ ⚠ same type
DCBLD1 p.Ala182Val Uncertain significance ★ ⚠ same type
DCBLD1 p.Ala206Thr Uncertain significance ★ ⚠ same type
DCBLD1 p.Ala28Val Uncertain significance ★ ⚠ same type
DCBLD1 p.Ala479Asp Uncertain significance ★ ⚠ same type
DCBLD1 p.Ala509Ser 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/dcbld1-p-pro63arg (accessed [today's date]).

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