Is PCGF2 p.Pro342His (c.1025C>A) pathogenic?

PCGF2 p.Pro342His (c.1025C>A) is classified Conflicting classifications of pathogenicity in PCGF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-30). AlphaMissense: likely benign (0.1089); Ultra-rare (popmax 0.037%, mid); Associated with Inborn genetic diseases.

What condition is associated with PCGF2 p.Pro342His (c.1025C>A)?

PCGF2 p.Pro342His (c.1025C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PCGF2 p.Pro342His (c.1025C>A) in the general population?

PCGF2 p.Pro342His (c.1025C>A) is ultra-rare (popmax 0.037%, mid) (gnomAD).

What do computational predictors say about PCGF2 p.Pro342His (c.1025C>A)?

AlphaMissense predicts likely benign (score 0.1089) — an in-silico prediction, not a clinical call.

PCGF2 p.Pro342His

c.1025C>A · rs770193210 · VCV1560211

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1089 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.037%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1089	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Overall
CADD	26.2	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 0.037% Middle Eastern · 2/5,402 alleles

Filtering AF 0.00657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00266%

Overall 0.00231% 33/1,428,412 alleles · ultra-rare exomes 31/1,276,250 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.037%	2,701
Admixed American	0.00543%	18,405
European (non-Finnish)	0.00241%	41,564
Remaining individualsnot grpmax-eligible	0.00184%	54,384
South Asian	0.00153%	65,288
African / African-American	0.00143%	69,822

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.Pro342His
Coding: c.1025C>A
MANE Select: NM_007144
dbSNP: rs770193210
Type: single nucleotide variant
Location: chr17:38735233 (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-pro342his (accessed [today's date]).

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