Is DCDC2 p.Val347Glu (c.1040T>A) pathogenic?

DCDC2 p.Val347Glu (c.1040T>A) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-22). AlphaMissense: likely pathogenic (0.6602); Very rare (popmax 0.00769%, sas).

How common is DCDC2 p.Val347Glu (c.1040T>A) in the general population?

DCDC2 p.Val347Glu (c.1040T>A) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about DCDC2 p.Val347Glu (c.1040T>A)?

AlphaMissense predicts likely pathogenic (score 0.6602) — an in-silico prediction, not a clinical call.

DCDC2 p.Val347Glu

c.1040T>A · VCV3764422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6602	likely pathogenic
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	25.2	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 0.00769% South Asian · 7/91,018 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000548% 8/1,460,728 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,003
European (non-Finnish)	8.48e-05%	1,179,728

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: DCDC2
Protein: p.Val347Glu
Coding: c.1040T>A
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24178616 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 347: a UniProt-annotated variant site (in nsc); the 'disordered' region

Full DCDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC2 p.Val347Leu Uncertain significance ★ ⚠ same residue
DCDC2 c.294-2A>G Pathogenic ★★ same type
DCDC2 c.349-2A>G Pathogenic ★★ same type
DCDC2 c.705-2A>G Pathogenic ★★ same type
DCDC2 p.Leu297Ter Pathogenic ★★ same type
DCDC2 p.Met1Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
DCDC2 p.Ser128Ter Pathogenic/Likely pathogenic ★★ same type
DCDC2 p.Ala153Gly 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/dcdc2-p-val347glu (accessed [today's date]).

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