Is PCGF2 p.Arg235Trp (c.703C>T) pathogenic?

PCGF2 p.Arg235Trp (c.703C>T) is classified Likely benign in PCGF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-31). AlphaMissense: likely pathogenic (0.621); Very rare (popmax 0.00533%, amr); Associated with Inborn genetic diseases.

What condition is associated with PCGF2 p.Arg235Trp (c.703C>T)?

PCGF2 p.Arg235Trp (c.703C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCGF2 p.Arg235Trp (c.703C>T) in the general population?

PCGF2 p.Arg235Trp (c.703C>T) is very rare (popmax 0.00533%, amr) (gnomAD).

What do computational predictors say about PCGF2 p.Arg235Trp (c.703C>T)?

AlphaMissense predicts likely pathogenic (score 0.621) — an in-silico prediction, not a clinical call.

PCGF2 p.Arg235Trp

c.703C>T · rs200143494 · VCV2080640

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.621	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -13.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.2	GERP -1.6, phastCons 1
Overall
CADD	25.6	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 0.00533% Admixed American · 3/56,320 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000841%

Overall 0.00177% 28/1,584,984 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00652%	15,335
Admixed Americangrpmax	0.00533%	18,773
East Asian	0.00458%	21,822
European (non-Finnish)	0.00163%	61,306

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg235Trp
Coding: c.703C>T
MANE Select: NM_001136498 · reported on NM_007144
dbSNP: rs200143494
Type: single nucleotide variant
Location: chr17:38735555 (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-arg235trp (accessed [today's date]).

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