Is PHF8 p.Phe379= (c.1137T>C) pathogenic?

PHF8 p.Phe379= (c.1137T>C) is classified Uncertain significance in PHF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability Siderius type.

What condition is associated with PHF8 p.Phe379= (c.1137T>C)?

PHF8 p.Phe379= (c.1137T>C) is associated with syndromic X-linked intellectual disability Siderius type (ClinVar).

How common is PHF8 p.Phe379= (c.1137T>C) in the general population?

PHF8 p.Phe379= (c.1137T>C) is absent from gnomAD v4.1 (gnomAD).

PHF8 p.Phe379=

c.1137T>C · VCV4056713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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.
REVEL	0.292	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -3.8, phastCons 1
Overall
CADD	10.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHF8
Protein: p.Phe379=
Coding: c.1137T>C
MANE Select: NM_015107
Type: single nucleotide variant
Location: chrX:54002159 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB
Residue 379: the jmjc domain; an α-helix

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.Arg240Ter Likely pathogenic ★★ same condition
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-phe379 (accessed [today's date]).

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