Is PCGF2 p.Pro65Ser (c.193C>T) pathogenic?

PCGF2 p.Pro65Ser (c.193C>T) is classified Likely pathogenic in PCGF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-12). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with turnpenny-fry syndrome.

What condition is associated with PCGF2 p.Pro65Ser (c.193C>T)?

PCGF2 p.Pro65Ser (c.193C>T) is associated with turnpenny-fry syndrome (ClinVar).

How common is PCGF2 p.Pro65Ser (c.193C>T) in the general population?

PCGF2 p.Pro65Ser (c.193C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCGF2 p.Pro65Ser (c.193C>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

PCGF2 p.Pro65Ser

c.193C>T · rs1567941256 · VCV624617

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

turnpenny-fry syndrome

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic ✓ concordant with ClinVar · top 7% in PCGF2
REVEL	0.315	indeterminate
SaProt	LLR -14.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	27.4	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: PCGF2
Protein: p.Pro65Ser
Coding: c.193C>T
MANE Select: NM_007144
dbSNP: rs1567941256
Type: single nucleotide variant
Location: chr17:38739602 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.30
Residue 65: a UniProt-annotated variant site (in tpfs)

Full PCGF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

turnpenny-fry syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCGF2 p.Pro65Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
PCGF2 p.Pro65= Likely benign ★★ same residue
PCGF2 p.Pro65Arg Likely pathogenic ★ same residue
PCGF2 p.Glu198Lys Uncertain significance ★★ ⚠ same condition
PCGF2 p.Gly221Arg Uncertain significance ★★ ⚠ same condition
PCGF2 p.Asp145= Benign ★★ same condition
PCGF2 p.Asp210Gly Uncertain significance ★ ⚠ same condition
PCGF2 p.Asn50fs 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/pcgf2-p-pro65ser (accessed [today's date]).

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