Is DCBLD2 p.Ala482Asp (c.1445C>A) pathogenic?

DCBLD2 p.Ala482Asp (c.1445C>A) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.1374); Rare (popmax 0.151%, nfe).

How common is DCBLD2 p.Ala482Asp (c.1445C>A) in the general population?

DCBLD2 p.Ala482Asp (c.1445C>A) is rare (popmax 0.151%, nfe) (gnomAD).

What do computational predictors say about DCBLD2 p.Ala482Asp (c.1445C>A)?

AlphaMissense predicts likely benign (score 0.1374) — an in-silico prediction, not a clinical call.

DCBLD2 p.Ala482Asp

c.1445C>A · rs143662022 · VCV2212203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1374 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1374	likely benign
REVEL	0.498	indeterminate
SaProt	LLR -9.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.0054 · regional, not allelic
Overall
CADD	21.2	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 0.151% European (non-Finnish) · 1,786/1,179,620 alleles

Filtering AF 0.146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.131% 2,120/1,613,492 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.466%	214
European (non-Finnish)grpmax	0.151%	660
Remaining individualsnot grpmax-eligible	0.133%	752
Middle Eastern	0.0991%	1,009
Finnishnot grpmax-eligible	0.0656%	1,523
Admixed American	0.045%	2,221
South Asian	0.0253%	3,959
African / African-American	0.02%	5,000

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala482Asp
Coding: c.1445C>A
MANE Select: NM_080927
dbSNP: rs143662022
Type: single nucleotide variant
Location: chr3:98811473 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13
Residue 482: the 'disordered' region

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.Ala5Ser 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-ala482asp (accessed [today's date]).

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