Is DCDC2B p.Ser283Thr (c.847T>A) pathogenic?

DCDC2B p.Ser283Thr (c.847T>A) is classified Uncertain significance in DCDC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.0764); Ultra-rare (popmax 0.052%, afr).

How common is DCDC2B p.Ser283Thr (c.847T>A) in the general population?

DCDC2B p.Ser283Thr (c.847T>A) is ultra-rare (popmax 0.052%, afr) (gnomAD).

What do computational predictors say about DCDC2B p.Ser283Thr (c.847T>A)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

DCDC2B p.Ser283Thr

c.847T>A · VCV3271040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -1.6, phastCons 0.18
Regional constraint	o/e 1.06	unconstrained · MANE · 6,800 bp · p 0.21 · regional, not allelic
Overall
CADD	8.747	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 0.052% African / African-American · 39/74,974 alleles

Filtering AF 0.039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0345%

Overall 0.00254% 41/1,613,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.052%	1,922
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: DCDC2B
Protein: p.Ser283Thr
Coding: c.847T>A
MANE Select: NM_001099434
Type: single nucleotide variant
Location: chr1:32214929 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.12

Full DCDC2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC2B p.Ala125Pro Uncertain significance ★ ⚠ same type
DCDC2B p.Ala187Gly Uncertain significance ★ ⚠ same type
DCDC2B p.Ala239Ser Uncertain significance ★ ⚠ same type
DCDC2B p.Ala291Thr Uncertain significance ★ ⚠ same type
DCDC2B p.Ala346Val Uncertain significance ★ ⚠ same type
DCDC2B p.Ala55Ser Uncertain significance ★ ⚠ same type
DCDC2B p.Ala55Val Uncertain significance ★ ⚠ same type
DCDC2B p.Ala69Glu 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/dcdc2b-p-ser283thr (accessed [today's date]).

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