Is PHF8 p.Phe312= (c.936C>T) pathogenic?

PHF8 p.Phe312= (c.936C>T) is classified Likely benign in PHF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-06). Ultra-rare (popmax 0.0391%, amr); Associated with Inborn genetic diseases.

What condition is associated with PHF8 p.Phe312= (c.936C>T)?

PHF8 p.Phe312= (c.936C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHF8 p.Phe312= (c.936C>T) in the general population?

PHF8 p.Phe312= (c.936C>T) is ultra-rare (popmax 0.0391%, amr) (gnomAD).

PHF8 p.Phe312=

c.936C>T · rs782190302 · VCV1766699

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0391%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.345	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.46, phastCons 1
Overall
CADD	12.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0391% Admixed American · 18/46,011 alleles

Filtering AF 0.0252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00157% 19/1,210,504 alleles · ultra-rare exomes 19/1,096,723 · genomes 0/113,781 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0391%	2,556
European (non-Finnish)	0.000112%	894,286

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.Phe312=
Coding: c.936C>T
MANE Select: NM_015107
dbSNP: rs782190302
Type: single nucleotide variant
Location: chrX:54011132 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB
Residue 312: the jmjc domain; an α-helix

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-phe312 (accessed [today's date]).

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