Is STIL p.Ser690= (c.2070A>T) pathogenic?

STIL p.Ser690= (c.2070A>T) is classified Conflicting classifications of pathogenicity in STIL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2019-12-31). Ultra-rare (popmax 0.0312%, eas).

How common is STIL p.Ser690= (c.2070A>T) in the general population?

STIL p.Ser690= (c.2070A>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

STIL p.Ser690=

c.2070A>T · rs367887740 · VCV287268

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, 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 0.2	GERP -4.2, phastCons 0.99
Overall
CADD	6.469	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,892 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00384% 62/1,614,076 alleles · ultra-rare exomes 46/1,461,894 · genomes 16/152,182 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0528%	1,894
East Asiangrpmax	0.0312%	3,207
Admixed American	0.0233%	4,286
European (non-Finnish)	8.47e-05%	1,180,034

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser690=
Coding: c.2070A>T
MANE Select: NM_001048166
dbSNP: rs367887740
Type: single nucleotide variant
Location: chr1:47280388 (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 690: the 'interaction with rbm14' region; the 'interaction with cpap' region; the 'pin1-binding' 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-ser690 (accessed [today's date]).

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