Is DCDC2B p.Ala346Val (c.1037C>T) pathogenic?

DCDC2B p.Ala346Val (c.1037C>T) is classified Uncertain significance in DCDC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely benign (0.0887); Very rare (popmax 0.00589%, amr).

How common is DCDC2B p.Ala346Val (c.1037C>T) in the general population?

DCDC2B p.Ala346Val (c.1037C>T) is very rare (popmax 0.00589%, amr) (gnomAD).

What do computational predictors say about DCDC2B p.Ala346Val (c.1037C>T)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

DCDC2B p.Ala346Val

c.1037C>T · VCV4009703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00589%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.84	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 0.45	GERP -0.7
Regional constraint	o/e 1.06	unconstrained · MANE · 6,800 bp · p 0.21 · regional, not allelic
Overall
CADD	13.28	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 0.00589% Admixed American · 3/50,940 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.00174% 27/1,551,082 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00589%	16,980
European (non-Finnish)	0.00192%	52,137
Remaining individualsnot grpmax-eligible	0.00166%	60,084
African / African-American	0.00137%	72,924

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.Ala346Val
Coding: c.1037C>T
MANE Select: NM_001099434
Type: single nucleotide variant
Location: chr1:32215884 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.12
Residue 346: the 'disordered' region

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.Ala55Ser Uncertain significance ★ ⚠ same type
DCDC2B p.Ala55Val Uncertain significance ★ ⚠ same type
DCDC2B p.Ala69Glu Uncertain significance ★ ⚠ same type
DCDC2B p.Ala69Thr 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-ala346val (accessed [today's date]).

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