Is STIL p.Ser484= (c.1452C>G) pathogenic?

STIL p.Ser484= (c.1452C>G) is classified Benign in STIL (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-30). Common (popmax 35.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Ser484= (c.1452C>G)?

STIL p.Ser484= (c.1452C>G) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

STIL p.Ser484=

Q: How common is STIL p.Ser484= (c.1452C>G) in the general population?

STIL p.Ser484= (c.1452C>G) is common (popmax 35.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1452C>G · rs10789505 · VCV160051

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 35.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.114	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 0.39
Overall
CADD	5.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.6% African / African-American · 26,662/74,906 alleles

Filtering AF 35.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.1%

Overall 10.4% 168,087/1,613,872 alleles · common exomes 143,303/1,461,800 · genomes 24,784/152,072 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	35.6%	3
East Asian	33.4%	3
South Asian	17.1%	6
Amishnot grpmax-eligible	13.8%	7
Remaining individualsnot grpmax-eligible	11.5%	9
Middle Eastern	10.1%	10
Ashkenazi Jewishnot grpmax-eligible	9%	11
European (non-Finnish)	7.88%	13
Admixed American	6.4%	16
Finnishnot grpmax-eligible	5.48%	18

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.Ser484=
Coding: c.1452C>G
MANE Select: NM_001048166
dbSNP: rs10789505
Type: single nucleotide variant
Location: chr1:47281006 (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 484: the 'interaction with rbm14' region; the 'interaction with cpap' region

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

Disease context

microcephaly 7, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STIL c.*203C>T Uncertain significance ★★ same condition
STIL c.*599A>G Uncertain significance ★★ same condition
STIL p.Ala543Val Uncertain significance ★★ ⚠ same condition
STIL p.Arg742His Uncertain significance ★★ ⚠ same condition
STIL p.Arg9Gln Uncertain significance ★★ ⚠ same condition
STIL p.Asp1192Asn Uncertain significance ★★ ⚠ same condition
STIL p.Asp631Glu Uncertain significance ★★ ⚠ same condition
STIL p.Cys503Gly Uncertain significance ★★ ⚠ same condition

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-ser484 (accessed [today's date]).

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