Is STIL p.Ala86Val (c.257C>T) pathogenic?

STIL p.Ala86Val (c.257C>T) is classified Benign in STIL (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0486); Common (popmax 83.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 7, primary, autosomal recessive.

What condition is associated with STIL p.Ala86Val (c.257C>T)?

STIL p.Ala86Val (c.257C>T) is associated with microcephaly 7, primary, autosomal recessive (ClinVar).

What do computational predictors say about STIL p.Ala86Val (c.257C>T)?

AlphaMissense predicts likely benign (score 0.0486) — an in-silico prediction, not a clinical call.

STIL p.Ala86Val

Q: How common is STIL p.Ala86Val (c.257C>T) in the general population?

STIL p.Ala86Val (c.257C>T) is common (popmax 83.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.257C>T · rs3125630 · VCV21354

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0486 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 83.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 7, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0486	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -3.83	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 9.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	17.43	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 83.9% African / African-American · 62,775/74,808 alleles

Filtering AF 83.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 83.1%

Overall 50.1% 805,467/1,606,720 alleles · common exomes 718,056/1,454,740 · genomes 87,411/151,980 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	83.9%	1
East Asian	57.8%	2
Admixed American	56%	2
Amishnot grpmax-eligible	53.2%	2
Remaining individualsnot grpmax-eligible	49.8%	2
European (non-Finnish)	48.8%	2
Middle Eastern	47.2%	2
South Asian	46.3%	2
Finnishnot grpmax-eligible	36.1%	3
Ashkenazi Jewishnot grpmax-eligible	35.3%	3

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.Ala86Val
Coding: c.257C>T
MANE Select: NM_001048166
dbSNP: rs3125630
Type: single nucleotide variant
Location: chr1:47302242 (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 86: the 'interaction with rbm14' region; a UniProt-annotated variant site (in)

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-ala86val (accessed [today's date]).

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