Is PCGF2 p.Pro102Ser (c.304C>T) pathogenic?

PCGF2 p.Pro102Ser (c.304C>T) is classified Uncertain significance in PCGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-14). AlphaMissense: ambiguous (0.4794); Very rare (popmax 0.00667%, amr).

How common is PCGF2 p.Pro102Ser (c.304C>T) in the general population?

PCGF2 p.Pro102Ser (c.304C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about PCGF2 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts ambiguous (score 0.4794) — an in-silico prediction, not a clinical call.

PCGF2 p.Pro102Ser

c.304C>T · rs764992830 · VCV1945366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4794	ambiguous
REVEL	0.275	benign-leaning
SaProt	LLR -13.29	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	23.5	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

Grpmax group 0.00667% Admixed American · 4/60,012 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000496% 8/1,613,260 alleles · very rare exomes 8/1,461,022 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,003
European (non-Finnish)	0.000339%	294,998

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.Pro102Ser
Coding: c.304C>T
MANE Select: NM_007144
dbSNP: rs764992830
Type: single nucleotide variant
Location: chr17:38739080 (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

Similar variants

PCGF2 p.Pro65Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
PCGF2 p.Pro65Ser Likely pathogenic ★★ same type
PCGF2 p.Ala212Thr Uncertain significance ★★ ⚠ same type
PCGF2 p.Arg45Cys Uncertain significance ★★ ⚠ same type
PCGF2 p.Glu136Asp Uncertain significance ★★ ⚠ same type
PCGF2 p.Glu198Lys Uncertain significance ★★ ⚠ same type
PCGF2 p.Gly115Ser Uncertain significance ★★ ⚠ same type
PCGF2 p.Gly221Arg 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-pro102ser (accessed [today's date]).

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