Is STIL p.Ser418Pro (c.1252T>C) pathogenic?

STIL p.Ser418Pro (c.1252T>C) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). AlphaMissense: likely benign (0.0985); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with STIL p.Ser418Pro (c.1252T>C)?

STIL p.Ser418Pro (c.1252T>C) is associated with Inborn genetic diseases (ClinVar).

How common is STIL p.Ser418Pro (c.1252T>C) in the general population?

STIL p.Ser418Pro (c.1252T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STIL p.Ser418Pro (c.1252T>C)?

AlphaMissense predicts likely benign (score 0.0985) — an in-silico prediction, not a clinical call.

STIL p.Ser418Pro

c.1252T>C · rs2524047817 · VCV2621786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0985	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.06	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 6	GERP 0.95, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	19.85	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STIL
Protein: p.Ser418Pro
Coding: c.1252T>C
MANE Select: NM_001048166
dbSNP: rs2524047817
Type: single nucleotide variant
Location: chr1:47281206 (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 418: 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-ser418pro (accessed [today's date]).

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