Is PHF20 p.Pro297Ser (c.889C>T) pathogenic?

PHF20 p.Pro297Ser (c.889C>T) is classified Uncertain significance in PHF20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1713); Ultra-rare (popmax 0.0236%, amr).

How common is PHF20 p.Pro297Ser (c.889C>T) in the general population?

PHF20 p.Pro297Ser (c.889C>T) is ultra-rare (popmax 0.0236%, amr) (gnomAD).

What do computational predictors say about PHF20 p.Pro297Ser (c.889C>T)?

AlphaMissense predicts likely benign (score 0.1713) — an in-silico prediction, not a clinical call.

PHF20 p.Pro297Ser

c.889C>T · VCV3888257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1713	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 116 kb · p 3.5e-12 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0236% Admixed American · 14/59,444 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.00193% 31/1,608,242 alleles · ultra-rare exomes 29/1,456,262 · genomes 2/151,980 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0236%	4,246
Remaining individualsnot grpmax-eligible	0.00963%	10,385
African / African-American	0.00268%	37,353
European (non-Finnish)	0.000765%	130,681

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.Pro297Ser
Coding: c.889C>T
MANE Select: NM_016436
Type: single nucleotide variant
Location: chr20:35869518 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.32 · 7 PDB
Residue 297: the 'disordered' region

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

Similar variants

PHF20 p.Pro297Leu Likely pathogenic ⚠ same residue
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

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-pro297ser (accessed [today's date]).

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