Is STIL p.Ser1052= (c.3156C>T) pathogenic?

STIL p.Ser1052= (c.3156C>T) is classified Conflicting classifications of pathogenicity in STIL (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-21). Rare (popmax 0.1%, afr).

How common is STIL p.Ser1052= (c.3156C>T) in the general population?

STIL p.Ser1052= (c.3156C>T) is rare (popmax 0.1%, afr) (gnomAD).

STIL p.Ser1052=

c.3156C>T · rs113337758 · VCV497987

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, afr)

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 0.7	GERP -1.8, phastCons 0.95
Overall
CADD	8.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% African / African-American · 75/74,816 alleles

Filtering AF 0.0819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.021% 337/1,607,536 alleles · rare exomes 273/1,455,250 · genomes 64/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.1%	998
Middle Eastern	0.0997%	1,003
Remaining individualsnot grpmax-eligible	0.0691%	1,446
Admixed American	0.0645%	1,551
European (non-Finnish)	0.0148%	6,766
South Asian	0.00112%	89,654

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.Ser1052=
Coding: c.3156C>T
MANE Select: NM_001048166
dbSNP: rs113337758
Type: single nucleotide variant
Location: chr1:47251847 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 54.29 · 5 PDB

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-ser1052 (accessed [today's date]).

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