Is AGGF1 p.Pro6Arg (c.17C>G) pathogenic?

AGGF1 p.Pro6Arg (c.17C>G) is classified Uncertain significance in AGGF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.0936); Very rare (popmax 0.00308%, nfe).

How common is AGGF1 p.Pro6Arg (c.17C>G) in the general population?

AGGF1 p.Pro6Arg (c.17C>G) is very rare (popmax 0.00308%, nfe) (gnomAD).

What do computational predictors say about AGGF1 p.Pro6Arg (c.17C>G)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

AGGF1 p.Pro6Arg

c.17C>G · VCV4023884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00308%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -7.39	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 0.35	GERP -2.8, phastCons 0.021
Regional constraint	o/e 1.02	unconstrained · MANE · 5,858 bp · p 0.71 · regional, not allelic
Overall
CADD	12.84	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 0.00308% European (non-Finnish) · 36/1,169,808 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.002%

Overall 0.0024% 38/1,583,034 alleles · very rare exomes 36/1,430,822 · genomes 2/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00308%	32,495
East Asian	0.00229%	43,666
Remaining individualsnot grpmax-eligible	0.00163%	61,530

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: AGGF1
Protein: p.Pro6Arg
Coding: c.17C>G
MANE Select: NM_018046
Type: single nucleotide variant
Location: chr5:77030783 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.24
Residue 6: the 'disordered' region

Full AGGF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGGF1 p.Pro6Gln Uncertain significance ★ ⚠ same residue
AGGF1 c.313+6T>C Benign ★★ same type
AGGF1 p.Glu133Lys Benign/Likely benign ★★ same type
AGGF1 p.Met706Leu Benign ★★ same type
AGGF1 p.Tyr112Cys Likely benign ★★ same type
AGGF1 p.Tyr382= Benign/Likely benign ★★ same type
AGGF1 p.Ala314Thr Uncertain significance ★ ⚠ same type
AGGF1 p.Ala385Val 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/aggf1-p-pro6arg (accessed [today's date]).

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