Is PHF8 p.Val147= (c.441T>G) pathogenic?

PHF8 p.Val147= (c.441T>G) is classified Benign in PHF8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Low-frequency (popmax 3.57%, mid); Associated with Inborn genetic diseases.

What condition is associated with PHF8 p.Val147= (c.441T>G)?

PHF8 p.Val147= (c.441T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PHF8 p.Val147= (c.441T>G) in the general population?

PHF8 p.Val147= (c.441T>G) is low-frequency (popmax 3.57%, mid) (gnomAD).

PHF8 p.Val147=

c.441T>G · rs148215758 · VCV129890

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.57%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	phastCons 1
Overall
CADD	9.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.57% Middle Eastern · 155/4,340 alleles

Filtering AF 3.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.42%

Overall 3.03% 36,592/1,206,266 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.87%	21
Middle Easterngrpmax	3.57%	28
European (non-Finnish)	3.47%	29
Amishnot grpmax-eligible	2.94%	34
Remaining individualsnot grpmax-eligible	2.62%	38
Ashkenazi Jewishnot grpmax-eligible	1.92%	52
Admixed American	1.43%	70
South Asian	1.17%	85
African / African-American	0.402%	249
East Asian	0.00296%	33,747

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val147=
Coding: c.441T>G
MANE Select: NM_015107
dbSNP: rs148215758
Type: single nucleotide variant
Location: chrX:54017674 (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-val147 (accessed [today's date]).

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