Is PGF p.Cys160Arg (c.478T>C) pathogenic?

PGF p.Cys160Arg (c.478T>C) is classified Uncertain significance in PGF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). Ultra-rare (popmax 0.0147%, afr).

How common is PGF p.Cys160Arg (c.478T>C) in the general population?

PGF p.Cys160Arg (c.478T>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

PGF p.Cys160Arg

c.478T>C · VCV4135295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.347	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.71, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,900 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000682% 11/1,613,734 alleles · ultra-rare exomes 5/1,461,568 · genomes 6/152,166 · 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: PGF
Protein: p.Cys160Arg
Coding: c.478T>C
MANE Select: NM_002632
Type: single nucleotide variant
Location: chr14:74946220 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 71.00 · 2 PDB

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

Similar variants

PIGF p.Ile160Val Uncertain significance ★ ⚠ same residue
PIGF p.Cys83Trp Uncertain significance ★★ same type
PIGF p.Val62Ala Benign ★★ same type
PGF p.Ala21Thr Uncertain significance ★ ⚠ same type
PGF p.Ala54Val Uncertain significance ★ ⚠ same type
PGF p.Arg110Leu Uncertain significance ★ ⚠ same type
PGF p.Arg114Trp Uncertain significance ★ ⚠ same type
PGF p.Arg127Cys 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/pgf-p-cys160arg (accessed [today's date]).

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