Is DCBLD2 p.Ala182Thr (c.544G>A) pathogenic?

DCBLD2 p.Ala182Thr (c.544G>A) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.2351); Ultra-rare (popmax 0.036%, nfe).

How common is DCBLD2 p.Ala182Thr (c.544G>A) in the general population?

DCBLD2 p.Ala182Thr (c.544G>A) is ultra-rare (popmax 0.036%, nfe) (gnomAD).

What do computational predictors say about DCBLD2 p.Ala182Thr (c.544G>A)?

AlphaMissense predicts likely benign (score 0.2351) — an in-silico prediction, not a clinical call.

DCBLD2 p.Ala182Thr

c.544G>A · rs180752673 · VCV2346947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2351 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2351	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 76 kb · p 0.018 · regional, not allelic
Overall
CADD	27.1	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 0.036% European (non-Finnish) · 425/1,179,846 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.0283% 456/1,613,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.036%	2,776
Remaining individualsnot grpmax-eligible	0.0304%	3,288
African / African-American	0.00933%	10,715
Admixed American	0.00833%	12,002

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.Ala182Thr
Coding: c.544G>A
MANE Select: NM_080927
dbSNP: rs180752673
Type: single nucleotide variant
Location: chr3:98849488 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13
Residue 182: the cub 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.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
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-ala182thr (accessed [today's date]).

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