Is PHF6 p.Thr78= (c.234G>A) pathogenic?

PHF6 p.Thr78= (c.234G>A) is classified Conflicting classifications of pathogenicity in PHF6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-24). Very rare (popmax 0.00351%, afr); Associated with Borjeson-Forssman-Lehmann syndrome.

What condition is associated with PHF6 p.Thr78= (c.234G>A)?

PHF6 p.Thr78= (c.234G>A) is associated with Borjeson-Forssman-Lehmann syndrome (ClinVar).

How common is PHF6 p.Thr78= (c.234G>A) in the general population?

PHF6 p.Thr78= (c.234G>A) is very rare (popmax 0.00351%, afr) (gnomAD).

PHF6 p.Thr78=

c.234G>A · rs1160852520 · VCV2848186

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00351%, afr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.3
Overall
CADD	2.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00351% African / African-American · 2/57,039 alleles

Filtering AF 0.000582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000288%

Overall 0.000938% 11/1,173,093 alleles · very rare exomes 11/1,059,949 · genomes 0/113,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00351%	28,520
Remaining individualsnot grpmax-eligible	0.00216%	46,262
European (non-Finnish)	0.000926%	107,966

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: PHF6
Protein: p.Thr78=
Coding: c.234G>A
MANE Select: NM_001015877
dbSNP: rs1160852520
Type: single nucleotide variant
Location: chrX:134378100 (GRCh38)
Structure: AlphaFold pLDDT 73.45 · 2 PDB
Residue 78: the 'extended phd1 domain (ephd1)' 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 p.Thr78Met Uncertain significance ★★ ⚠ same residue
PHF6 p.Arg116Ter Pathogenic ★★ same condition
PHF6 p.Arg225Ter Pathogenic ★★ same condition
PHF6 p.Arg274Ter Pathogenic ★★ same condition
PHF6 p.Arg342Ter Pathogenic ★★ same condition
PHF6 p.Cys45Tyr Pathogenic ★★ same condition
PHF6 p.Met1Thr Pathogenic ★★ same condition
PHF6 p.Arg163His 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-thr78 (accessed [today's date]).

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