Is PCGF2 p.Ser71Phe (c.212C>T) pathogenic?

PCGF2 p.Ser71Phe (c.212C>T) is classified Uncertain significance in PCGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-04). AlphaMissense: likely pathogenic (0.871); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PCGF2 p.Ser71Phe (c.212C>T)?

PCGF2 p.Ser71Phe (c.212C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCGF2 p.Ser71Phe (c.212C>T) in the general population?

PCGF2 p.Ser71Phe (c.212C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PCGF2 p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely pathogenic (score 0.871) — an in-silico prediction, not a clinical call.

PCGF2 p.Ser71Phe

c.212C>T · VCV4133085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.871 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.871	likely pathogenic
REVEL	0.17	moderately benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	26.3	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 8.48e-05% European (non-Finnish) · 1/1,179,868 alleles

Overall 0.000657% 1/152,156 alleles · very rare

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.Ser71Phe
Coding: c.212C>T
MANE Select: NM_007144
Type: single nucleotide variant
Location: chr17:38739251 (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

Disease context

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

Similar variants

PCGF2 p.Ala212Thr Uncertain significance ★★ ⚠ same condition
PCGF2 p.Arg45Cys Uncertain significance ★★ ⚠ same condition
PCGF2 p.Glu136Asp Uncertain significance ★★ ⚠ same condition
PCGF2 p.Gly115Ser Uncertain significance ★★ ⚠ same condition
PCGF2 p.Gly315Arg Uncertain significance ★★ ⚠ same condition
PCGF2 p.His2Pro Uncertain significance ★★ ⚠ same condition
PCGF2 p.Val58Met Uncertain significance ★★ ⚠ same condition
PCGF2 p.Arg114Cys Benign/Likely benign ★★ ⚠ same condition

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-ser71phe (accessed [today's date]).

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