Is DCDC2B p.Arg31His (c.92G>A) pathogenic?

DCDC2B p.Arg31His (c.92G>A) is classified Uncertain significance in DCDC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely benign (0.1117); Rare (popmax 0.178%, eas).

How common is DCDC2B p.Arg31His (c.92G>A) in the general population?

DCDC2B p.Arg31His (c.92G>A) is rare (popmax 0.178%, eas) (gnomAD).

What do computational predictors say about DCDC2B p.Arg31His (c.92G>A)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

DCDC2B p.Arg31His

c.92G>A · VCV3838508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.178%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -0.039, phastCons 0.87
Regional constraint	o/e 1.06	unconstrained · MANE · 6,800 bp · p 0.21 · regional, not allelic
Overall
CADD	22.1	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 0.178% East Asian · 80/44,876 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.0057% 92/1,614,000 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.178%	561
Admixed American	0.00333%	30,014
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,078
European (non-Finnish)	0.000678%	147,485

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.Arg31His
Coding: c.92G>A
MANE Select: NM_001099434
Type: single nucleotide variant
Location: chr1:32209185 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.12
Residue 31: the doublecortin 1 domain

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

Similar variants

DCDC2B p.Arg31Cys 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-arg31his (accessed [today's date]).

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