Is PHF2 p.Lys890= (c.2670G>A) pathogenic?

PHF2 p.Lys890= (c.2670G>A) is classified Likely benign in PHF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 0.00401%, afr); Associated with PHF2-related disorder.

What condition is associated with PHF2 p.Lys890= (c.2670G>A)?

PHF2 p.Lys890= (c.2670G>A) is associated with PHF2-related disorder (ClinVar).

How common is PHF2 p.Lys890= (c.2670G>A) in the general population?

PHF2 p.Lys890= (c.2670G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

PHF2 p.Lys890=

c.2670G>A · VCV3351708

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

PHF2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP -3.3, phastCons 1
Overall
CADD	6.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,906 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,790 alleles · very rare exomes 3/1,461,680 · genomes 2/152,110 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,969
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	8.47e-05%	1,179,966

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: PHF2
Protein: p.Lys890=
Coding: c.2670G>A
MANE Select: NM_005392
Type: single nucleotide variant
Location: chr9:93674970 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.14 · 9 PDB
Residue 890: the 'disordered' region

Full PHF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHF2-related disorder

Similar variants

PHF2 p.Gly527Ser Uncertain significance ★ ⚠ same condition
PHF2 p.Ser1020Thr Uncertain significance ★ ⚠ same condition
PHF2 p.Asp133= Likely benign same condition
PHF2 p.Gly629= Likely benign same condition
PHF2 p.His865= Likely benign same condition
PHF2 p.Leu548= Benign same condition
PHF2 p.Pro273= Likely benign same condition
PHF2 p.Pro480Leu Likely benign 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/phf2-p-lys890 (accessed [today's date]).

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