Is PHF20 p.Ser562Arg (c.1686T>G) pathogenic?

PHF20 p.Ser562Arg (c.1686T>G) is classified Uncertain significance in PHF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: ambiguous (0.3467); Very rare (popmax 0.00133%, afr).

How common is PHF20 p.Ser562Arg (c.1686T>G) in the general population?

PHF20 p.Ser562Arg (c.1686T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PHF20 p.Ser562Arg (c.1686T>G)?

AlphaMissense predicts ambiguous (score 0.3467) — an in-silico prediction, not a clinical call.

PHF20 p.Ser562Arg

c.1686T>G · VCV3888266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3467 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3467	ambiguous
REVEL	0.056	moderately benign-leaning
SaProt	LLR -7.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 116 kb · p 3.5e-12 · regional, not allelic
Overall
CADD	19.34	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,908 alleles

Overall 6.2e-05% 1/1,614,016 alleles · very rare exomes 0/1,461,876 · genomes 1/152,140 · joint denominator

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: PHF20
Protein: p.Ser562Arg
Coding: c.1686T>G
MANE Select: NM_016436
Type: single nucleotide variant
Location: chr20:35914058 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.32 · 7 PDB
Residue 562: the 'disordered' region

Full PHF20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHF20 c.1826-4G>A Benign ★★ same type
PHF20 c.2897-6C>T Benign/Likely benign ★★ same type
PHF20 p.Arg845= Benign ★★ same type
PHF20 p.Phe621= Benign ★★ same type
PHF20 p.Pro827= Benign ★★ same type
PHF20 p.Ala235Asp Uncertain significance ★ ⚠ same type
PHF20 p.Ala395Val Uncertain significance ★ ⚠ same type
PHF20 p.Ala443Thr Uncertain significance ★ ⚠ same type

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/phf20-p-ser562arg (accessed [today's date]).

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