Is STIL p.Arg9Trp (c.25C>T) pathogenic?

STIL p.Arg9Trp (c.25C>T) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1232); Very rare (popmax 0.005%, amr); Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Arg9Trp (c.25C>T)?

STIL p.Arg9Trp (c.25C>T) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

How common is STIL p.Arg9Trp (c.25C>T) in the general population?

STIL p.Arg9Trp (c.25C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about STIL p.Arg9Trp (c.25C>T)?

AlphaMissense predicts likely benign (score 0.1232) — an in-silico prediction, not a clinical call.

STIL p.Arg9Trp

c.25C>T · rs762659511 · VCV297568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1232 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1232	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP -3.2
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	14.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,960 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000682% 11/1,612,596 alleles · very rare exomes 8/1,460,518 · genomes 3/152,078 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,987
Remaining individualsnot grpmax-eligible	0.0016%	62,422
Finnishnot grpmax-eligible	0.00157%	63,556
African / African-American	0.00134%	74,862
South Asian	0.0011%	91,048
European (non-Finnish)	0.000339%	294,850

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.Arg9Trp
Coding: c.25C>T
MANE Select: NM_001048166
dbSNP: rs762659511
Type: single nucleotide variant
Location: chr1:47310295 (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 9: the 'interaction with rbm14' 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 p.Arg9Gln Uncertain significance ★★ ⚠ same residue
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.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-arg9trp (accessed [today's date]).

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