Is PHF20 p.Pro63Ser (c.187C>T) pathogenic?

PHF20 p.Pro63Ser (c.187C>T) is classified Uncertain significance in PHF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely pathogenic (0.8466); Absent from gnomAD v4.1.

How common is PHF20 p.Pro63Ser (c.187C>T) in the general population?

PHF20 p.Pro63Ser (c.187C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHF20 p.Pro63Ser (c.187C>T)?

AlphaMissense predicts likely pathogenic (score 0.8466) — an in-silico prediction, not a clinical call.

PHF20 p.Pro63Ser

c.187C>T · rs2515954250 · VCV2612349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8466 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8466	likely pathogenic
REVEL	0.296	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.008, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 116 kb · p 3.5e-12 · regional, not allelic
Overall
CADD	27.2	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

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: PHF20
Protein: p.Pro63Ser
Coding: c.187C>T
MANE Select: NM_016436
dbSNP: rs2515954250
Type: single nucleotide variant
Location: chr20:35842676 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.32 · 7 PDB
Residue 63: the tudor 1 domain

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-pro63ser (accessed [today's date]).

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