Is STIL p.Pro28= (c.84A>G) pathogenic?

STIL p.Pro28= (c.84A>G) is classified Likely benign in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 0.00669%, eas).

How common is STIL p.Pro28= (c.84A>G) in the general population?

STIL p.Pro28= (c.84A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

STIL p.Pro28=

c.84A>G · rs572125774 · VCV740175

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP 2.3, phastCons 1
Overall
CADD	11.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,868 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000743% 12/1,614,090 alleles · very rare exomes 10/1,461,812 · genomes 2/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,956
South Asian	0.00659%	15,179
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000169%	589,998

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: STIL
Protein: p.Pro28=
Coding: c.84A>G
MANE Select: NM_001048166
dbSNP: rs572125774
Type: single nucleotide variant
Location: chr1:47304957 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 54.29 · 5 PDB
Residue 28: the 'interaction with rbm14' region

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

Similar variants

STIL c.*203C>T Uncertain significance ★★ same type
STIL c.*599A>G Uncertain significance ★★ same type
STIL p.Ala213Val Uncertain significance ★★ ⚠ same type
STIL p.Ala543Val Uncertain significance ★★ ⚠ same type
STIL p.Arg1004Gly Uncertain significance ★★ ⚠ same type
STIL p.Arg67Cys Uncertain significance ★★ ⚠ same type
STIL p.Arg742His Uncertain significance ★★ ⚠ same type
STIL p.Arg9Gln 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/stil-p-pro28 (accessed [today's date]).

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