Is PHF8 p.Gln802Pro (c.2405A>C) pathogenic?

PHF8 p.Gln802Pro (c.2405A>C) is classified Uncertain significance in PHF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-18). AlphaMissense: likely benign (0.3228); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PHF8 p.Gln802Pro (c.2405A>C)?

PHF8 p.Gln802Pro (c.2405A>C) is associated with Inborn genetic diseases (ClinVar).

How common is PHF8 p.Gln802Pro (c.2405A>C) in the general population?

PHF8 p.Gln802Pro (c.2405A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHF8 p.Gln802Pro (c.2405A>C)?

AlphaMissense predicts likely benign (score 0.3228) — an in-silico prediction, not a clinical call.

PHF8 p.Gln802Pro

c.2405A>C · rs1569526703 · VCV588359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3228 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3228	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 44 kb · p 7.9e-07 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q838P vs ClinVar Q802P) — 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.Gln802Pro
Coding: c.2405A>C
MANE Select: NM_015107
dbSNP: rs1569526703
Type: single nucleotide variant
Location: chrX:53984952 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB
Residue 838 UniProt numbering: 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-gln802pro (accessed [today's date]).

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