Is DCBLD2 p.Ala341Thr (c.1021G>A) pathogenic?

DCBLD2 p.Ala341Thr (c.1021G>A) is classified Uncertain significance in DCBLD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely benign (0.3143); Ultra-rare (popmax 0.0666%, mid).

How common is DCBLD2 p.Ala341Thr (c.1021G>A) in the general population?

DCBLD2 p.Ala341Thr (c.1021G>A) is ultra-rare (popmax 0.0666%, mid) (gnomAD).

What do computational predictors say about DCBLD2 p.Ala341Thr (c.1021G>A)?

AlphaMissense predicts likely benign (score 0.3143) — an in-silico prediction, not a clinical call.

DCBLD2 p.Ala341Thr

c.1021G>A · rs200822370 · VCV2350349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3143 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0666%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3143	likely benign
REVEL	0.599	indeterminate
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 23 kb · p 0.0054 · regional, not allelic
Overall
CADD	26.5	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 0.0666% Middle Eastern · 4/6,010 alleles

Filtering AF 0.0377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.0338% 545/1,611,736 alleles · ultra-rare exomes 498/1,459,500 · genomes 47/152,236 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0666%	1,503
Remaining individualsnot grpmax-eligible	0.0417%	2,401
European (non-Finnish)	0.0407%	2,456
Admixed American	0.0218%	4,581
South Asian	0.0165%	6,048
Finnishnot grpmax-eligible	0.00469%	21,301
African / African-American	0.004%	24,995
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,548

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.Ala341Thr
Coding: c.1021G>A
MANE Select: NM_080927
dbSNP: rs200822370
Type: single nucleotide variant
Location: chr3:98819268 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.13
Residue 341: 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.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-ala341thr (accessed [today's date]).

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