Is PGF p.Arg169Trp (c.505C>T) pathogenic?

PGF p.Arg169Trp (c.505C>T) is classified Uncertain significance in PGF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.1719); Ultra-rare (popmax 0.0308%, sas).

How common is PGF p.Arg169Trp (c.505C>T) in the general population?

PGF p.Arg169Trp (c.505C>T) is ultra-rare (popmax 0.0308%, sas) (gnomAD).

What do computational predictors say about PGF p.Arg169Trp (c.505C>T)?

AlphaMissense predicts likely benign (score 0.1719) — an in-silico prediction, not a clinical call.

PGF p.Arg169Trp

c.505C>T · rs202127516 · VCV2373623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1719 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1719	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP -1.9, phastCons 0.98
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R220W vs ClinVar R169W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0308% South Asian · 28/90,932 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00478% 77/1,611,770 alleles · ultra-rare exomes 69/1,459,506 · genomes 8/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0308%	3,248
Admixed American	0.0118%	8,507
Remaining individualsnot grpmax-eligible	0.00962%	10,396
African / African-American	0.00669%	14,953
East Asian	0.00448%	22,308
European (non-Finnish)	0.00237%	42,111
Finnishnot grpmax-eligible	0.00156%	63,938

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.Arg169Trp
Coding: c.505C>T
MANE Select: NM_002632
dbSNP: rs202127516
Type: single nucleotide variant
Location: chr14:74942714 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 71.00 · 2 PDB
Residue 220 UniProt numbering: the 'disordered' region

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

Similar variants

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
PGF p.Arg127His 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-arg169trp (accessed [today's date]).

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