Is INTS9 p.Ala286Asp (c.857C>A) pathogenic?

INTS9 p.Ala286Asp (c.857C>A) is classified Uncertain significance in INTS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely pathogenic (0.9846); Absent from gnomAD v4.1.

How common is INTS9 p.Ala286Asp (c.857C>A) in the general population?

INTS9 p.Ala286Asp (c.857C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS9 p.Ala286Asp (c.857C>A)?

AlphaMissense predicts likely pathogenic (score 0.9846) — an in-silico prediction, not a clinical call.

INTS9 p.Ala286Asp

c.857C>A · rs2487215998 · VCV2620589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9846 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9846	likely pathogenic
REVEL	0.328	indeterminate
SaProt	LLR -12.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 19 kb · p 5.8e-07 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INTS9
Protein: p.Ala286Asp
Coding: c.857C>A
MANE Select: NM_018250
dbSNP: rs2487215998
Type: single nucleotide variant
Location: chr8:28793987 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.95 · 15 PDB
Residue 286: an α-helix

Full INTS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS9 p.Leu417Pro Uncertain significance ★★ ⚠ same type
INTS9 p.Ala208Val Uncertain significance ★ ⚠ same type
INTS9 p.Ala319Val Uncertain significance ★ ⚠ same type
INTS9 p.Ala506Thr Uncertain significance ★ ⚠ same type
INTS9 p.Ala560Thr Uncertain significance ★ ⚠ same type
INTS9 p.Arg401Cys Uncertain significance ★ ⚠ same type
INTS9 p.Arg401His Uncertain significance ★ ⚠ same type
INTS9 p.Arg500Gln 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/ints9-p-ala286asp (accessed [today's date]).

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