Is STIL p.Pro350Ser (c.1048C>T) pathogenic?

STIL p.Pro350Ser (c.1048C>T) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely benign (0.0853); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with STIL p.Pro350Ser (c.1048C>T)?

STIL p.Pro350Ser (c.1048C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STIL p.Pro350Ser (c.1048C>T) in the general population?

STIL p.Pro350Ser (c.1048C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about STIL p.Pro350Ser (c.1048C>T)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

STIL p.Pro350Ser

c.1048C>T · VCV3963213

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -3.75	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 3.5	GERP -0.27, phastCons 0.88
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	15.75	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 0.00134% African / African-American · 1/74,882 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00093% 15/1,613,398 alleles · very rare exomes 13/1,461,270 · genomes 2/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,882
European (non-Finnish)	0.00119%	84,264

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.Pro350Ser
Coding: c.1048C>T
MANE Select: NM_001048166
Type: single nucleotide variant
Location: chr1:47287636 (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 350: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STIL p.Ala213Val Uncertain significance ★★ ⚠ same condition
STIL p.Ala543Val Uncertain significance ★★ ⚠ same condition
STIL p.Arg1004Gly Uncertain significance ★★ ⚠ same condition
STIL p.Arg67Cys Uncertain significance ★★ ⚠ same condition
STIL p.Arg742His Uncertain significance ★★ ⚠ same condition
STIL p.Arg9Gln Uncertain significance ★★ ⚠ same condition
STIL p.Asn72Ser Uncertain significance ★★ ⚠ same condition
STIL p.Asp1192Asn 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-pro350ser (accessed [today's date]).

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