Is PHF6 p.Ser256del (c.766_768del) pathogenic?

PHF6 p.Ser256del (c.766768del) is classified Uncertain significance in PHF6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-28). No gnomAD frequency available for this variant; Associated with Borjeson-Forssman-Lehmann syndrome.

What condition is associated with PHF6 p.Ser256del (c.766_768del)?

PHF6 p.Ser256del (c.766_768del) is associated with Borjeson-Forssman-Lehmann syndrome (ClinVar).

How common is PHF6 p.Ser256del (c.766_768del) in the general population?

PHF6 p.Ser256del (c.766_768del) is no gnomAD frequency available for this variant (gnomAD).

PHF6 p.Ser256del

c.766_768del · rs2520636040 · VCV2833295

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Borjeson-Forssman-Lehmann syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8	GERP 2.6, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHF6
Protein: p.Ser256del
Coding: c.766_768del
MANE Select: NM_001015877
dbSNP: rs2520636040
Type: Deletion
Location: chrX:134415050 (GRCh38)
Structure: AlphaFold pLDDT 73.45 · 2 PDB
Residue 256: the 'extended phd2 domain (ephd2)' region

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

Disease context

Borjeson-Forssman-Lehmann syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHF6 c.139-11_139-7del Benign/Likely benign ★★ same condition
PHF6 p.Arg277fs Pathogenic ★ same condition
PHF6 p.Lys310_Ala311insTer Likely pathogenic ★ same condition
PHF6 p.Glu341del Uncertain significance ★ same condition
PHF6 p.Lys38fs Uncertain significance ★ same condition
PHF6 p.Ser256Leu Uncertain significance ★ ⚠ same residue
PHF6 c.139-13del Likely benign ★ same condition
PHF6 c.374+16_374+20del 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/phf6-p-ser256del (accessed [today's date]).

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