Is PCGF2 p.Arg331Cys (c.991C>T) pathogenic?

PCGF2 p.Arg331Cys (c.991C>T) is classified Uncertain significance in PCGF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). AlphaMissense: ambiguous (0.4195); Ultra-rare (popmax 0.0543%, mid); Associated with Inborn genetic diseases.

What condition is associated with PCGF2 p.Arg331Cys (c.991C>T)?

PCGF2 p.Arg331Cys (c.991C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCGF2 p.Arg331Cys (c.991C>T) in the general population?

PCGF2 p.Arg331Cys (c.991C>T) is ultra-rare (popmax 0.0543%, mid) (gnomAD).

What do computational predictors say about PCGF2 p.Arg331Cys (c.991C>T)?

AlphaMissense predicts ambiguous (score 0.4195) — an in-silico prediction, not a clinical call.

PCGF2 p.Arg331Cys

c.991C>T · rs1906600599 · VCV2285890

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0543%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4195	ambiguous
REVEL	0.075	moderately benign-leaning
SaProt	LLR -8.73	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.4	GERP 2.3, phastCons 1
Overall
CADD	24.7	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 0.0543% Middle Eastern · 3/5,524 alleles

Filtering AF 0.0147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.0019% 25/1,314,564 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0543%	1,841
European (non-Finnish)	0.00191%	52,313
African / African-American	0.0014%	71,482

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.Arg331Cys
Coding: c.991C>T
MANE Select: NM_001136498 · reported on NM_007144
dbSNP: rs1906600599
Type: single nucleotide variant
Location: chr17:38735267 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg331cys (accessed [today's date]).

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