Is PHF8 p.Arg240Ter (c.718C>T) pathogenic?

PHF8 p.Arg240Ter (c.718C>T) is classified Likely pathogenic in PHF8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-29). No allele count reported in gnomAD v4.1 (AN 1,204,155); Associated with syndromic X-linked intellectual disability Siderius type.

What condition is associated with PHF8 p.Arg240Ter (c.718C>T)?

PHF8 p.Arg240Ter (c.718C>T) is associated with syndromic X-linked intellectual disability Siderius type (ClinVar).

How common is PHF8 p.Arg240Ter (c.718C>T) in the general population?

PHF8 p.Arg240Ter (c.718C>T) is no allele count reported in gnomAD v4.1 (AN 1,204,155) (gnomAD).

PHF8 p.Arg240Ter

c.718C>T · VCV4280332

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,204,155)

Conditions

syndromic X-linked intellectual disability Siderius type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 22
REVEL	0.571	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,204,155). 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: PHF8
Protein: p.Arg240Ter
Coding: c.718C>T
MANE Select: NM_015107
Type: single nucleotide variant
Location: chrX:54014442 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB
Residue 240: the jmjc domain

Full PHF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

syndromic X-linked intellectual disability Siderius type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHF8 p.Arg240Gln Uncertain significance ★★ ⚠ same residue
PHF8 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same condition
PHF8 p.Arg753Ter Pathogenic/Likely pathogenic ★★ same condition
PHF8 p.Arg66His Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg753Gln Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg773Pro Uncertain significance ★★ ⚠ same condition
PHF8 p.Leu949Phe Uncertain significance ★★ ⚠ same condition
PHF8 p.Tyr706Cys 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/phf8-p-arg240ter (accessed [today's date]).

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