Is STIL p.Pro1143= (c.3429C>T) pathogenic?

STIL p.Pro1143= (c.3429C>T) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2013-10-30). Ultra-rare (popmax 0.0227%, afr); Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Pro1143= (c.3429C>T)?

STIL p.Pro1143= (c.3429C>T) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

How common is STIL p.Pro1143= (c.3429C>T) in the general population?

STIL p.Pro1143= (c.3429C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

STIL p.Pro1143=

c.3429C>T · rs144628824 · VCV160064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -5.2
Overall
CADD	5.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,858 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00186% 30/1,613,658 alleles · ultra-rare exomes 22/1,461,532 · genomes 8/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,403
Remaining individualsnot grpmax-eligible	0.0032%	31,237
Finnishnot grpmax-eligible	0.00156%	64,014
European (non-Finnish)	0.000848%	117,986

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.Pro1143=
Coding: c.3429C>T
MANE Select: NM_001048166
dbSNP: rs144628824
Type: single nucleotide variant
Location: chr1:47251574 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 54.29 · 5 PDB

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-pro1143 (accessed [today's date]).

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