Is PCGF2 p.Asp145= (c.435C>T) pathogenic?

PCGF2 p.Asp145= (c.435C>T) is classified Benign in PCGF2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 51%, afr) — too common for a highly-penetrant pathogenic allele; Associated with turnpenny-fry syndrome.

What condition is associated with PCGF2 p.Asp145= (c.435C>T)?

PCGF2 p.Asp145= (c.435C>T) is associated with turnpenny-fry syndrome (ClinVar).

PCGF2 p.Asp145=

Q: How common is PCGF2 p.Asp145= (c.435C>T) in the general population?

PCGF2 p.Asp145= (c.435C>T) is common (popmax 51%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.435C>T · rs1138349 · VCV1326991

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 51%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

turnpenny-fry syndrome

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 -3.2	GERP -2.5
Overall
CADD	4.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51% African / African-American · 37,496/73,582 alleles

Filtering AF 50.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 50.3%

Overall 45.9% 721,653/1,572,030 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	51%	2
European (non-Finnish)	46.6%	2
South Asian	46.6%	2
Finnishnot grpmax-eligible	46.5%	2
Remaining individualsnot grpmax-eligible	46.4%	2
Middle Eastern	45.2%	2
Amishnot grpmax-eligible	40.9%	2
Admixed American	38.4%	3
Ashkenazi Jewishnot grpmax-eligible	38.3%	3
East Asian	31.3%	3

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: PCGF2
Protein: p.Asp145=
Coding: c.435C>T
MANE Select: NM_007144
dbSNP: rs1138349
Type: single nucleotide variant
Location: chr17:38738586 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.30

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 condition
PCGF2 p.Pro65Ser Likely pathogenic ★★ same condition
PCGF2 p.Glu198Lys Uncertain significance ★★ ⚠ same condition
PCGF2 p.Gly221Arg Uncertain significance ★★ ⚠ same condition
PCGF2 p.Asp210Gly Uncertain significance ★ ⚠ same condition
PCGF2 p.Asn50fs Uncertain significance ★ same condition
PCGF2 p.Ala212Thr Uncertain significance ★★ ⚠ same type
PCGF2 p.Arg45Cys 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/pcgf2-p-asp145 (accessed [today's date]).

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