Is PHF8 p.Pro783Ser (c.2347C>T) pathogenic?

PHF8 p.Pro783Ser (c.2347C>T) is classified Uncertain significance in PHF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: ambiguous (0.3929); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PHF8 p.Pro783Ser (c.2347C>T)?

PHF8 p.Pro783Ser (c.2347C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHF8 p.Pro783Ser (c.2347C>T) in the general population?

PHF8 p.Pro783Ser (c.2347C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHF8 p.Pro783Ser (c.2347C>T)?

AlphaMissense predicts ambiguous (score 0.3929) — an in-silico prediction, not a clinical call.

PHF8 p.Pro783Ser

c.2347C>T · VCV3417726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3929	ambiguous
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.90	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 156 bp · p 0.44 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P819S vs ClinVar P783S) — verify the residue.

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.Pro783Ser
Coding: c.2347C>T
MANE Select: NM_015107
Type: single nucleotide variant
Location: chrX:53985010 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB
Residue 783: the 'disordered' region

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-pro783ser (accessed [today's date]).

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