Is PCGF2 p.Pro341Ser (c.1021C>T) pathogenic?

PCGF2 p.Pro341Ser (c.1021C>T) is classified Uncertain significance in PCGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-02). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.00267%, nfe).

How common is PCGF2 p.Pro341Ser (c.1021C>T) in the general population?

PCGF2 p.Pro341Ser (c.1021C>T) is very rare (popmax 0.00267%, nfe) (gnomAD).

What do computational predictors say about PCGF2 p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

PCGF2 p.Pro341Ser

c.1021C>T · VCV3718954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP -2.3, phastCons 1
Overall
CADD	18.33	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 0.00267% European (non-Finnish) · 29/1,086,702 alleles

Filtering AF 0.00187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00208% 30/1,441,154 alleles · very rare exomes 29/1,289,002 · genomes 1/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00267%	37,473
African / African-American	0.00142%	70,322

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.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_007144
Type: single nucleotide variant
Location: chr17:38735237 (GRCh38)

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

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-pro341ser (accessed [today's date]).

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