Is PGF p.Arg127Cys (c.379C>T) pathogenic?

PGF p.Arg127Cys (c.379C>T) is classified Uncertain significance in PGF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.3114); Ultra-rare (popmax 0.0113%, eas).

How common is PGF p.Arg127Cys (c.379C>T) in the general population?

PGF p.Arg127Cys (c.379C>T) is ultra-rare (popmax 0.0113%, eas) (gnomAD).

What do computational predictors say about PGF p.Arg127Cys (c.379C>T)?

AlphaMissense predicts likely benign (score 0.3114) — an in-silico prediction, not a clinical call.

PGF p.Arg127Cys

c.379C>T · VCV3888054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3114 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3114	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -13.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.69, phastCons 0.95
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic
Overall
CADD	21.9	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 0.0113% East Asian · 5/44,088 alleles

Filtering AF 0.00561% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0052%

Overall 0.00589% 94/1,595,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0113%	8,818
European (non-Finnish)	0.00686%	14,573
Admixed American	0.00506%	19,771
South Asian	0.00333%	30,023
Remaining individualsnot grpmax-eligible	0.00325%	30,802
African / African-American	0.00134%	74,496

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.Arg127Cys
Coding: c.379C>T
MANE Select: NM_002632
Type: single nucleotide variant
Location: chr14:74948520 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 71.00 · 2 PDB
Residue 127: a disulfide bond; a β-strand

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

Similar variants

PGF p.Arg127His 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.Arg134Gln 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-arg127cys (accessed [today's date]).

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