Is DCBLD2 p.Arg427His (c.1280G>A) pathogenic?

DCBLD2 p.Arg427His (c.1280G>A) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.2353); Very rare (popmax 0.00401%, afr).

How common is DCBLD2 p.Arg427His (c.1280G>A) in the general population?

DCBLD2 p.Arg427His (c.1280G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DCBLD2 p.Arg427His (c.1280G>A)?

AlphaMissense predicts likely benign (score 0.2353) — an in-silico prediction, not a clinical call.

DCBLD2 p.Arg427His

c.1280G>A · VCV3838488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2353 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2353	likely benign
REVEL	0.921	moderately pathogenic-leaning
SaProt	LLR -11.71	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.0054 · regional, not allelic
Overall
CADD	32.0	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 0.00401% African / African-American · 3/74,860 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000868% 14/1,613,306 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,953
Remaining individualsnot grpmax-eligible	0.0032%	31,217
Finnishnot grpmax-eligible	0.00313%	31,985
South Asian	0.0022%	45,538
Admixed American	0.00167%	59,940
European (non-Finnish)	0.000339%	294,903

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.Arg427His
Coding: c.1280G>A
MANE Select: NM_080927
Type: single nucleotide variant
Location: chr3:98812415 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13
Residue 427: a disulfide bond; the f5/8 type c domain

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-arg427his (accessed [today's date]).

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