Is STIL p.Ser556Phe (c.1667C>T) pathogenic?

STIL p.Ser556Phe (c.1667C>T) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1371); Absent from gnomAD v4.1; Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Ser556Phe (c.1667C>T)?

STIL p.Ser556Phe (c.1667C>T) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

How common is STIL p.Ser556Phe (c.1667C>T) in the general population?

STIL p.Ser556Phe (c.1667C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STIL p.Ser556Phe (c.1667C>T)?

AlphaMissense predicts likely benign (score 0.1371) — an in-silico prediction, not a clinical call.

STIL p.Ser556Phe

c.1667C>T · rs752376811 · VCV297560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1371 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.1371	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -7.41	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 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	23.1	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.Ser556Phe
Coding: c.1667C>T
MANE Select: NM_001048166
dbSNP: rs752376811
Type: single nucleotide variant
Location: chr1:47280791 (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 556: 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-ser556phe (accessed [today's date]).

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