Is PHF6 p.Ala238= (c.714C>T) pathogenic?

PHF6 p.Ala238= (c.714C>T) is classified Benign in PHF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-21). Ultra-rare (popmax 0.074%, sas); Associated with Borjeson-Forssman-Lehmann syndrome.

What condition is associated with PHF6 p.Ala238= (c.714C>T)?

PHF6 p.Ala238= (c.714C>T) is associated with Borjeson-Forssman-Lehmann syndrome (ClinVar).

How common is PHF6 p.Ala238= (c.714C>T) in the general population?

PHF6 p.Ala238= (c.714C>T) is ultra-rare (popmax 0.074%, sas) (gnomAD).

PHF6 p.Ala238=

c.714C>T · rs761180935 · VCV796280

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.074%, sas)

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 -0.19	GERP -4.7, phastCons 0.002
Overall
CADD	3.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.074% South Asian · 42/56,730 alleles

Filtering AF 0.0562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.05%

Overall 0.00356% 43/1,207,577 alleles · ultra-rare exomes 42/1,097,043 · genomes 1/110,534 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.074%	1,351
Remaining individualsnot grpmax-eligible	0.0021%	47,553

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.Ala238=
Coding: c.714C>T
MANE Select: NM_001015877
dbSNP: rs761180935
Type: single nucleotide variant
Location: chrX:134413951 (GRCh38)
Structure: AlphaFold pLDDT 73.45 · 2 PDB
Residue 238: a β-strand; 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 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
PHF6 p.Arg166Lys 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-ala238 (accessed [today's date]).

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