Is PGF p.Ser79Pro (c.235T>C) pathogenic?

PGF p.Ser79Pro (c.235T>C) is classified Uncertain significance in PGF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.0932); Ultra-rare (popmax 0.0668%, afr).

How common is PGF p.Ser79Pro (c.235T>C) in the general population?

PGF p.Ser79Pro (c.235T>C) is ultra-rare (popmax 0.0668%, afr) (gnomAD).

What do computational predictors say about PGF p.Ser79Pro (c.235T>C)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

PGF p.Ser79Pro

c.235T>C · VCV4135292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic
Overall
CADD	15.06	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0668% African / African-American · 50/74,856 alleles

Filtering AF 0.052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0468%

Overall 0.00385% 62/1,612,324 alleles · ultra-rare exomes 26/1,460,158 · genomes 36/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0668%	1,497
Admixed American	0.0117%	8,543
Remaining individualsnot grpmax-eligible	0.00801%	12,481

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.Ser79Pro
Coding: c.235T>C
MANE Select: NM_002632
Type: single nucleotide variant
Location: chr14:74949437 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 71.00 · 2 PDB
Residue 79: a β-strand

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-ser79pro (accessed [today's date]).

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