Is INTS1 p.Thr506Ile (c.1517C>T) pathogenic?

INTS1 p.Thr506Ile (c.1517C>T) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely pathogenic (0.7844); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Thr506Ile (c.1517C>T)?

INTS1 p.Thr506Ile (c.1517C>T) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Thr506Ile (c.1517C>T) in the general population?

INTS1 p.Thr506Ile (c.1517C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS1 p.Thr506Ile (c.1517C>T)?

AlphaMissense predicts likely pathogenic (score 0.7844) — an in-silico prediction, not a clinical call.

INTS1 p.Thr506Ile

c.1517C>T · rs2483376858 · VCV2553683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7844 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7844	likely pathogenic
REVEL	0.242	benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	24.8	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

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: INTS1
Protein: p.Thr506Ile
Coding: c.1517C>T
MANE Select: NM_001080453
dbSNP: rs2483376858
Type: single nucleotide variant
Location: chr7:1497223 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB

Full INTS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS1 p.Thr506Ala Uncertain significance ★ ⚠ same residue
INTS1 c.1283+5G>A Uncertain significance ★★ same condition
INTS1 c.2977-5C>T Uncertain significance ★★ same condition
INTS1 p.Ala1505Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala1854Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2155Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2175Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala4Thr 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/ints1-p-thr506ile (accessed [today's date]).

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