Is DCDC2B p.Leu177Val (c.529C>G) pathogenic?

DCDC2B p.Leu177Val (c.529C>G) is classified Uncertain significance in DCDC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.1848); Very rare (popmax 0.00144%, nfe).

How common is DCDC2B p.Leu177Val (c.529C>G) in the general population?

DCDC2B p.Leu177Val (c.529C>G) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about DCDC2B p.Leu177Val (c.529C>G)?

AlphaMissense predicts likely benign (score 0.1848) — an in-silico prediction, not a clinical call.

DCDC2B p.Leu177Val

c.529C>G · VCV4009704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1848	likely benign
REVEL	0.604	indeterminate
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,800 bp · p 0.21 · regional, not allelic
Overall
CADD	28.7	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 0.00144% European (non-Finnish) · 17/1,179,800 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00105% 17/1,613,800 alleles · very rare

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.Leu177Val
Coding: c.529C>G
MANE Select: NM_001099434
Type: single nucleotide variant
Location: chr1:32212491 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.12
Residue 177: the doublecortin 2 domain

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

Similar variants

DCDC2B p.Leu177Phe Uncertain significance ★ ⚠ same residue
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

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-leu177val (accessed [today's date]).

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