Is PHF6 p.Val53= (c.159A>G) pathogenic?

PHF6 p.Val53= (c.159A>G) is classified Likely benign in PHF6 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-08-15). Very rare (popmax 0.00445%, amr); Associated with Inborn genetic diseases.

What condition is associated with PHF6 p.Val53= (c.159A>G)?

PHF6 p.Val53= (c.159A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PHF6 p.Val53= (c.159A>G) in the general population?

PHF6 p.Val53= (c.159A>G) is very rare (popmax 0.00445%, amr) (gnomAD).

PHF6 p.Val53=

c.159A>G · rs769976257 · VCV1776073

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00445%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -0.42, phastCons 0.9
Overall
CADD	5.525	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% Admixed American · 2/44,989 alleles

Filtering AF 0.000737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000584% 7/1,197,726 alleles · very rare exomes 7/1,084,547 · genomes 0/113,179 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00445%	22,495
South Asian	0.00367%	27,257
Remaining individualsnot grpmax-eligible	0.00212%	47,087
European (non-Finnish)	0.000225%	443,780

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: PHF6
Protein: p.Val53=
Coding: c.159A>G
MANE Select: NM_001015877
dbSNP: rs769976257
Type: single nucleotide variant
Location: chrX:134378025 (GRCh38)
Structure: AlphaFold pLDDT 73.45 · 2 PDB
Residue 53: the 'extended phd1 domain (ephd1)' region

Full PHF6 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

PHF6 p.Val53Leu Uncertain significance ★ ⚠ same residue
PHF6 p.Arg225Ter Pathogenic ★★ same condition
PHF6 p.Arg274Ter Pathogenic ★★ same condition
PHF6 p.Arg166Lys Uncertain significance ★★ ⚠ same condition
PHF6 p.Arg24Thr Uncertain significance ★★ ⚠ same condition
PHF6 p.Gln114His Uncertain significance ★★ ⚠ same condition
PHF6 p.Glu351Gly Uncertain significance ★★ ⚠ same condition
PHF6 p.His43Arg 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/phf6-p-val53 (accessed [today's date]).

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