Is STIL p.Phe299Ile (c.895T>A) pathogenic?

STIL p.Phe299Ile (c.895T>A) is classified Likely pathogenic in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). AlphaMissense: likely pathogenic (0.7641); Absent from gnomAD v4.1; Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Phe299Ile (c.895T>A)?

STIL p.Phe299Ile (c.895T>A) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

How common is STIL p.Phe299Ile (c.895T>A) in the general population?

STIL p.Phe299Ile (c.895T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STIL p.Phe299Ile (c.895T>A)?

AlphaMissense predicts likely pathogenic (score 0.7641) — an in-silico prediction, not a clinical call.

STIL p.Phe299Ile

c.895T>A · rs587784452 · VCV160069

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7641 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.7641	likely pathogenic ✓ concordant with ClinVar · top 9% in STIL
REVEL	0.463	indeterminate
SaProt	LLR -11.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

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.Phe299Ile
Coding: c.895T>A
MANE Select: NM_001048166
dbSNP: rs587784452
Type: single nucleotide variant
Location: chr1:47289563 (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 299: 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-phe299ile (accessed [today's date]).

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