Is DNMT3L p.His313= (c.939C>T) pathogenic?

DNMT3L p.His313= (c.939C>T) is classified Likely benign in DNMT3L (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Absent from gnomAD v4.1.

How common is DNMT3L p.His313= (c.939C>T) in the general population?

DNMT3L p.His313= (c.939C>T) is absent from gnomAD v4.1 (gnomAD).

DNMT3L p.His313=

c.939C>T · rs148066978 · VCV2652740

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.022	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -3.9
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

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: DNMT3L
Protein: p.His313=
Coding: c.939C>T
MANE Select: NM_175867
dbSNP: rs148066978
Type: single nucleotide variant
Location: chr21:44249082 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.47 · 29 PDB

Full DNMT3L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNMT3L p.Ala244Thr Uncertain significance ★ ⚠ same type
DNMT3L p.Ala270Thr Uncertain significance ★ ⚠ same type
DNMT3L p.Ala2Val Uncertain significance ★ ⚠ same type
DNMT3L p.Ala356Val Uncertain significance ★ ⚠ same type
DNMT3L p.Arg157Trp Uncertain significance ★ same type
DNMT3L p.Arg158Lys Uncertain significance ★ ⚠ same type
DNMT3L p.Arg161His Uncertain significance ★ ⚠ same type
DNMT3L p.Arg161Ser 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/dnmt3l-p-his313 (accessed [today's date]).

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