Is PHF6 p.Arg13= (c.39A>G) pathogenic?

PHF6 p.Arg13= (c.39A>G) is classified Likely benign in PHF6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-23). Very rare (popmax 0.00246%, nfe); Associated with PHF6-related disorder.

What condition is associated with PHF6 p.Arg13= (c.39A>G)?

PHF6 p.Arg13= (c.39A>G) is associated with PHF6-related disorder (ClinVar).

How common is PHF6 p.Arg13= (c.39A>G) in the general population?

PHF6 p.Arg13= (c.39A>G) is very rare (popmax 0.00246%, nfe) (gnomAD).

PHF6 p.Arg13=

c.39A>G · rs1259223307 · VCV3044070

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Conditions

PHF6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 22/894,832 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00182% 22/1,209,306 alleles · very rare exomes 19/1,097,724 · genomes 3/111,582 · joint denominator

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: PHF6
Protein: p.Arg13=
Coding: c.39A>G
MANE Select: NM_001015877
dbSNP: rs1259223307
Type: single nucleotide variant
Location: chrX:134377656 (GRCh38)
Structure: AlphaFold pLDDT 73.45 · 2 PDB

Full PHF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHF6-related disorder

Similar variants

PHF6 c.834+2T>G Likely pathogenic ★ same condition
PHF6 p.Gln14Ter Likely pathogenic ★ same condition
PHF6 p.Cys283Tyr Uncertain significance ★ ⚠ same condition
PHF6 p.Thr254Ile Uncertain significance ★ ⚠ same condition
PHF6 c.834+62T>C Uncertain significance same condition
PHF6 p.Cys87Tyr Uncertain significance ⚠ same condition
PHF6 p.His149Asn Uncertain significance ⚠ same condition
PHF6 p.Lys132Arg 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/phf6-p-arg13 (accessed [today's date]).

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