Is STIL p.Val97Ala (c.290T>C) pathogenic?

STIL p.Val97Ala (c.290T>C) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-24). AlphaMissense: ambiguous (0.4919); Very rare (popmax 0.00934%, afr).

How common is STIL p.Val97Ala (c.290T>C) in the general population?

STIL p.Val97Ala (c.290T>C) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about STIL p.Val97Ala (c.290T>C)?

AlphaMissense predicts ambiguous (score 0.4919) — an in-silico prediction, not a clinical call.

STIL p.Val97Ala

c.290T>C · rs886043449 · VCV286693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4919	ambiguous
REVEL	0.285	benign-leaning
SaProt	LLR -8.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense 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	24.0	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 0.00934% African / African-American · 7/74,932 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,613,928 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,705
European (non-Finnish)	8.47e-05%	1,180,012

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.Val97Ala
Coding: c.290T>C
MANE Select: NM_001048166
dbSNP: rs886043449
Type: single nucleotide variant
Location: chr1:47301724 (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 97: the 'interaction with rbm14' region

Full STIL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STIL c.*203C>T Uncertain significance ★★ same type
STIL c.*599A>G Uncertain significance ★★ same type
STIL p.Ala213Val Uncertain significance ★★ ⚠ same type
STIL p.Ala543Val Uncertain significance ★★ ⚠ same type
STIL p.Arg1004Gly Uncertain significance ★★ ⚠ same type
STIL p.Arg67Cys Uncertain significance ★★ ⚠ same type
STIL p.Arg742His Uncertain significance ★★ ⚠ same type
STIL p.Arg9Gln Uncertain significance ★★ ⚠ same type

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-val97ala (accessed [today's date]).

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