Is STIL p.Ser379Phe (c.1136C>T) pathogenic?

STIL p.Ser379Phe (c.1136C>T) is classified Conflicting classifications of pathogenicity in STIL (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.101); Rare (popmax 0.416%, nfe); Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Ser379Phe (c.1136C>T)?

STIL p.Ser379Phe (c.1136C>T) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

How common is STIL p.Ser379Phe (c.1136C>T) in the general population?

STIL p.Ser379Phe (c.1136C>T) is rare (popmax 0.416%, nfe) (gnomAD).

What do computational predictors say about STIL p.Ser379Phe (c.1136C>T)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

STIL p.Ser379Phe

c.1136C>T · rs149185431 · VCV160049

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.416%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.11	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 2.8	GERP -0.35, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	19.77	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

Grpmax group 0.416% European (non-Finnish) · 4,853/1,167,474 alleles

Filtering AF 0.406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.334% 5,347/1,598,892 alleles · rare exomes 4,974/1,446,624 · genomes 373/152,268 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.416%	241
Remaining individualsnot grpmax-eligible	0.281%	357
Admixed American	0.248%	403
African / African-American	0.0803%	1,246
Ashkenazi Jewishnot grpmax-eligible	0.0678%	1,476
South Asian	0.0606%	1,650
Finnishnot grpmax-eligible	0.0526%	1,900
Middle Eastern	0.0497%	2,011

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.Ser379Phe
Coding: c.1136C>T
MANE Select: NM_001048166
dbSNP: rs149185431
Type: single nucleotide variant
Location: chr1:47282457 (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 379: the 'interaction with rbm14' region; the 'interaction with cpap' region; the 'disordered' 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.Ser379= 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.Arg9Gln Uncertain significance ★★ ⚠ same condition
STIL p.Asp1192Asn Uncertain significance ★★ ⚠ same condition
STIL p.Asp631Glu 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-ser379phe (accessed [today's date]).

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