Is DNMT3B p.Arg310Ser (c.930G>C) pathogenic?

DNMT3B p.Arg310Ser (c.930G>C) is classified Uncertain significance in DNMT3B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-07). AlphaMissense: ambiguous (0.4246); Absent from gnomAD v4.1; Associated with DNMT3B-related disorder.

What condition is associated with DNMT3B p.Arg310Ser (c.930G>C)?

DNMT3B p.Arg310Ser (c.930G>C) is associated with DNMT3B-related disorder, immunodeficiency-centromeric instability-facial anomalies syndrome (ClinVar).

How common is DNMT3B p.Arg310Ser (c.930G>C) in the general population?

DNMT3B p.Arg310Ser (c.930G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNMT3B p.Arg310Ser (c.930G>C)?

AlphaMissense predicts ambiguous (score 0.4246) — an in-silico prediction, not a clinical call.

DNMT3B p.Arg310Ser

c.930G>C · rs772806134 · VCV853590

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4246 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

DNMT3B-related disorder

Computational evidence

Protein change
AlphaMissense	0.4246	ambiguous
REVEL	0.075	moderately benign-leaning
SaProt	LLR -4.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,534 bp · p 0.3 · regional, not allelic
Overall
CADD	14.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNMT3B
Protein: p.Arg310Ser
Coding: c.930G>C
MANE Select: NM_006892
dbSNP: rs772806134
Type: single nucleotide variant
Location: chr20:32792634 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 310: an α-helix

Full DNMT3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNMT3B-related disorder

Also linked: immunodeficiency-centromeric instability-facial anomalies syndrome

Similar variants

DNMT3B c.2421-11G>A Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Ala603Thr Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Arg826Cys Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Arg840Gln Likely pathogenic ★★ same condition
DNMT3B p.Asp653Asn Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.His814Arg Likely pathogenic ★★ ⚠ same condition
DNMT3B p.Val613Ala Pathogenic/Likely pathogenic ★★ same condition
DNMT3B p.Val726Gly Pathogenic/Likely pathogenic ★★ same condition

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/dnmt3b-p-arg310ser (accessed [today's date]).

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