Is DCBLD2 p.Ala667Thr (c.1999G>A) pathogenic?

DCBLD2 p.Ala667Thr (c.1999G>A) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: ambiguous (0.3779); Ultra-rare (popmax 0.0227%, afr).

How common is DCBLD2 p.Ala667Thr (c.1999G>A) in the general population?

DCBLD2 p.Ala667Thr (c.1999G>A) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about DCBLD2 p.Ala667Thr (c.1999G>A)?

AlphaMissense predicts ambiguous (score 0.3779) — an in-silico prediction, not a clinical call.

DCBLD2 p.Ala667Thr

c.1999G>A · rs767371934 · VCV3080382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Computational evidence

Protein change
AlphaMissense	0.3779	ambiguous
REVEL	0.325	indeterminate
SaProt	LLR -7.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.0054 · regional, not allelic
Overall
CADD	26.8	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 0.0227% African / African-American · 17/74,916 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00118% 19/1,613,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,407
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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.Ala667Thr
Coding: c.1999G>A
MANE Select: NM_080927
dbSNP: rs767371934
Type: single nucleotide variant
Location: chr3:98799701 (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.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-ala667thr (accessed [today's date]).

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