Is PHF8 p.Ser304= (c.912C>T) pathogenic?

PHF8 p.Ser304= (c.912C>T) is classified Likely benign in PHF8 (ClinVar, Single submitter, 2 submitters; last evaluated 2017-05-26). Ultra-rare (popmax 0.0131%, amr); Associated with Inborn genetic diseases.

What condition is associated with PHF8 p.Ser304= (c.912C>T)?

PHF8 p.Ser304= (c.912C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHF8 p.Ser304= (c.912C>T) in the general population?

PHF8 p.Ser304= (c.912C>T) is ultra-rare (popmax 0.0131%, amr) (gnomAD).

PHF8 p.Ser304=

c.912C>T · rs782306751 · VCV589586

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.29	GERP -5.8, phastCons 0.003
Overall
CADD	5.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0131% Admixed American · 6/45,971 alleles

Filtering AF 0.00567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00155% 17/1,096,545 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0131%	7,662
African / African-American	0.00173%	57,803
European (non-Finnish)	0.00112%	89,403

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: PHF8
Protein: p.Ser304=
Coding: c.912C>T
MANE Select: NM_015107
dbSNP: rs782306751
Type: single nucleotide variant
Location: chrX:54011156 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB
Residue 304: the jmjc domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHF8 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same condition
PHF8 p.Ala770Pro Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg240Gln Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg438His Uncertain significance ★★ same condition
PHF8 p.Arg588Gln Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg773Pro Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg968Cys Uncertain significance ★★ ⚠ same condition
PHF8 p.Arg982Trp 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-ser304 (accessed [today's date]).

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