Is PHF2 p.Lys447Arg (c.1340A>G) pathogenic?

PHF2 p.Lys447Arg (c.1340A>G) is classified Uncertain significance in PHF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.0932); Absent from gnomAD v4.1.

How common is PHF2 p.Lys447Arg (c.1340A>G) in the general population?

PHF2 p.Lys447Arg (c.1340A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHF2 p.Lys447Arg (c.1340A>G)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

PHF2 p.Lys447Arg

c.1340A>G · rs1826536012 · VCV2272265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 18 kb · p 7.2e-10 · regional, not allelic
Overall
CADD	24.7	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.

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: PHF2
Protein: p.Lys447Arg
Coding: c.1340A>G
MANE Select: NM_005392
dbSNP: rs1826536012
Type: single nucleotide variant
Location: chr9:93660202 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.14 · 9 PDB
Residue 447: the 'disordered' region

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

Similar variants

PHF2 c.299+7T>A Benign ★★ same type
PHF2 c.789+10G>A Benign/Likely benign ★★ same type
PHF2 p.Asp103= Benign ★★ same type
PHF2 p.Leu645= Benign/Likely benign ★★ same type
PHF2 p.Pro786= Benign ★★ same type
PHF2 p.Pro988= Benign ★★ same type
PHF2 p.Ser725= Benign ★★ same type
PHF2 p.Ser738= Benign ★★ 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/phf2-p-lys447arg (accessed [today's date]).

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