Is DNMT3B p.Phe843= (c.2529C>T) pathogenic?

DNMT3B p.Phe843= (c.2529C>T) is classified Conflicting classifications of pathogenicity in DNMT3B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-27). Rare (popmax 0.124%, afr); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 1.

What condition is associated with DNMT3B p.Phe843= (c.2529C>T)?

DNMT3B p.Phe843= (c.2529C>T) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 1, immunodeficiency-centromeric instability-facial anomalies syndrome (ClinVar).

How common is DNMT3B p.Phe843= (c.2529C>T) in the general population?

DNMT3B p.Phe843= (c.2529C>T) is rare (popmax 0.124%, afr) (gnomAD).

DNMT3B p.Phe843=

c.2529C>T · rs147402935 · VCV898981

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.124%, afr)

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.434	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.091	GERP 0.006, phastCons 0.93
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.124% African / African-American · 93/75,064 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.096%

Overall 0.01% 162/1,614,242 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.124%	807
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0176%	5,683
East Asian	0.0156%	6,413
European (non-Finnish)	0.00381%	26,223
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00167%	60,024
Finnishnot grpmax-eligible	0.00156%	64,044
South Asian	0.0011%	91,086

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: DNMT3B
Protein: p.Phe843=
Coding: c.2529C>T
MANE Select: NM_006892
dbSNP: rs147402935
Type: single nucleotide variant
Location: chr20:32807870 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.18 · 47 PDB
Residue 843: an α-helix; the sam-dependent mtase c5-type domain

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

Disease context

immunodeficiency-centromeric instability-facial anomalies syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-phe843 (accessed [today's date]).

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