Is PCGF2 p.Asp89Glu (c.267T>A) pathogenic?

PCGF2 p.Asp89Glu (c.267T>A) is classified Uncertain significance in PCGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-28). AlphaMissense: likely pathogenic (0.8025); Very rare (popmax 0.00439%, sas).

How common is PCGF2 p.Asp89Glu (c.267T>A) in the general population?

PCGF2 p.Asp89Glu (c.267T>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about PCGF2 p.Asp89Glu (c.267T>A)?

AlphaMissense predicts likely pathogenic (score 0.8025) — an in-silico prediction, not a clinical call.

PCGF2 p.Asp89Glu

c.267T>A · rs780159639 · VCV2420764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8025 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8025	likely pathogenic
REVEL	0.099	moderately benign-leaning
SaProt	LLR -10.73	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.60	acceptor gain · deltas
Pangolin	Δ0.50	gain · loss 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.4	GERP 0.96, phastCons 1
Overall
CADD	29.8	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 0.00439% South Asian · 4/91,030 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,611,332 alleles · very rare exomes 4/1,459,108 · genomes 0/152,224 · joint denominator

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.Asp89Glu
Coding: c.267T>A
MANE Select: NM_007144
dbSNP: rs780159639
Type: single nucleotide variant
Location: chr17:38739117 (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.Asp89Gly Uncertain significance ★ ⚠ same residue
PCGF2 p.Asp89= Likely benign ★ same residue
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

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-asp89glu (accessed [today's date]).

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