Is STIL p.Asp89Glu (c.267T>A) pathogenic?

STIL p.Asp89Glu (c.267T>A) is classified Uncertain significance in STIL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). AlphaMissense: ambiguous (0.3753); Ultra-rare (popmax 0.016%, afr).

How common is STIL p.Asp89Glu (c.267T>A) in the general population?

STIL p.Asp89Glu (c.267T>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about STIL p.Asp89Glu (c.267T>A)?

AlphaMissense predicts ambiguous (score 0.3753) — an in-silico prediction, not a clinical call.

STIL p.Asp89Glu

c.267T>A · rs766925193 · VCV1470103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3753	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -7.80	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.50	acceptor gain · deltas
Pangolin	Δ0.24	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.4	GERP -1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 59 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	32.0	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 0.016% African / African-American · 12/75,046 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.000991% 16/1,613,764 alleles · ultra-rare exomes 5/1,461,450 · genomes 11/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,254
Admixed American	0.005%	20,005
European (non-Finnish)	8.48e-05%	1,179,926

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.Asp89Glu
Coding: c.267T>A
MANE Select: NM_001048166
dbSNP: rs766925193
Type: single nucleotide variant
Location: chr1:47301747 (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 89: the 'interaction with rbm14' region

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

Similar variants

STIL p.Asp89Ala Uncertain significance ★ ⚠ same residue
STIL p.Asp89Gly Uncertain significance ★ ⚠ same residue
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

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-asp89glu (accessed [today's date]).

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