Is DNMT1 p.Val910Ala (c.2729T>C) pathogenic?

DNMT1 p.Val910Ala (c.2729T>C) is classified Uncertain significance in DNMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.0555); Very rare (popmax 6.84e-05%); Associated with DNMT1-related disorder.

What condition is associated with DNMT1 p.Val910Ala (c.2729T>C)?

DNMT1 p.Val910Ala (c.2729T>C) is associated with DNMT1-related disorder (ClinVar).

How common is DNMT1 p.Val910Ala (c.2729T>C) in the general population?

DNMT1 p.Val910Ala (c.2729T>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DNMT1 p.Val910Ala (c.2729T>C)?

AlphaMissense predicts likely benign (score 0.0555) — an in-silico prediction, not a clinical call.

DNMT1 p.Val910Ala

c.2729T>C · rs2513799212 · VCV2631910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DNMT1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0555	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.5
Regional constraint	o/e 0.96	unconstrained · MANE · 2,634 bp · p 0.67 · regional, not allelic
Overall
CADD	2.658	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V894A vs ClinVar V910A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,806 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: DNMT1
Protein: p.Val910Ala
Coding: c.2729T>C
MANE Select: NM_001130823
dbSNP: rs2513799212
Type: single nucleotide variant
Location: chr19:10146516 (GRCh38)
Gene constraint: LOEUF 0.15 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.88 · 29 PDB
Residue 894 UniProt numbering: an α-helix

Full DNMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNMT1-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNMT1 p.Val910Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DNMT1 p.Glu319Asp Uncertain significance ★★ ⚠ same condition
DNMT1 p.Lys307Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
DNMT1 p.Val972Met Conflicting classifications of pathogenicity ★ ⚠ same condition
DNMT1 p.Thr1204Ile Uncertain significance ⚠ same condition
DNMT1 c.494-6A>C Likely benign same condition
DNMT1 p.Tyr1273= Likely benign same condition
DNMT1 p.Asp329del Uncertain significance ★ 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/dnmt1-p-val910ala (accessed [today's date]).

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