Is STIL p.Ser356= (c.1068C>T) pathogenic?

STIL p.Ser356= (c.1068C>T) is classified Likely benign in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-15). Ultra-rare (popmax 0.01%, amr).

How common is STIL p.Ser356= (c.1068C>T) in the general population?

STIL p.Ser356= (c.1068C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

STIL p.Ser356=

c.1068C>T · rs138235440 · VCV2176535

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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 0.031	GERP -4.9
Overall
CADD	5.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,956 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00322% 52/1,613,072 alleles · ultra-rare exomes 44/1,460,822 · genomes 8/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,993
Remaining individualsnot grpmax-eligible	0.00641%	15,611
African / African-American	0.004%	25,001
European (non-Finnish)	0.00314%	31,878
East Asian	0.00223%	44,764
South Asian	0.0011%	90,934

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.Ser356=
Coding: c.1068C>T
MANE Select: NM_001048166
dbSNP: rs138235440
Type: single nucleotide variant
Location: chr1:47287616 (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 356: the 'interaction with rbm14' region; the 'interaction with cpap' 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-ser356 (accessed [today's date]).

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