Is PHF8 p.Asp609= (c.1827C>T) pathogenic?

PHF8 p.Asp609= (c.1827C>T) is classified Likely benign in PHF8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-11). Ultra-rare (popmax 0.0512%, sas); Associated with Inborn genetic diseases.

What condition is associated with PHF8 p.Asp609= (c.1827C>T)?

PHF8 p.Asp609= (c.1827C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHF8 p.Asp609= (c.1827C>T) in the general population?

PHF8 p.Asp609= (c.1827C>T) is ultra-rare (popmax 0.0512%, sas) (gnomAD).

PHF8 p.Asp609=

c.1827C>T · rs782251598 · VCV1780863

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.016	GERP -4.2, phastCons 0.021
Overall
CADD	0.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% South Asian · 29/56,587 alleles

Filtering AF 0.0366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0317%

Overall 0.00307% 37/1,205,821 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0512%	1,951
Remaining individualsnot grpmax-eligible	0.00632%	15,831
Finnishnot grpmax-eligible	0.00215%	46,472
European (non-Finnish)	0.000449%	222,943

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.Asp609=
Coding: c.1827C>T
MANE Select: NM_015107
dbSNP: rs782251598
Type: single nucleotide variant
Location: chrX:53987848 (GRCh38)
Structure: AlphaFold pLDDT 63.30 · 6 PDB

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-asp609 (accessed [today's date]).

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