Is INTS11 p.Thr182Ile (c.545C>T) pathogenic?

INTS11 p.Thr182Ile (c.545C>T) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.8746); Ultra-rare (popmax 0.0825%, eas).

How common is INTS11 p.Thr182Ile (c.545C>T) in the general population?

INTS11 p.Thr182Ile (c.545C>T) is ultra-rare (popmax 0.0825%, eas) (gnomAD).

What do computational predictors say about INTS11 p.Thr182Ile (c.545C>T)?

AlphaMissense predicts likely pathogenic (score 0.8746) — an in-silico prediction, not a clinical call.

INTS11 p.Thr182Ile

c.545C>T · rs764233397 · VCV2467438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8746	likely pathogenic
REVEL	0.645	pathogenic-leaning
SaProt	LLR -11.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.0825% East Asian · 37/44,824 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0543%

Overall 0.00242% 39/1,613,174 alleles · ultra-rare exomes 37/1,461,376 · genomes 2/151,798 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0825%	1,211
European (non-Finnish)	0.00017%	589,964

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: INTS11
Protein: p.Thr182Ile
Coding: c.545C>T
MANE Select: NM_017871
dbSNP: rs764233397
Type: single nucleotide variant
Location: chr1:1315422 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB

Full INTS11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS11 c.28+1406C>T Uncertain significance ★★ same type
INTS11 p.Ala241Thr Uncertain significance ★★ ⚠ same type
INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same type
INTS11 p.Gln467His Uncertain significance ★★ ⚠ same type
INTS11 p.Glu227Lys Uncertain significance ★★ same type
INTS11 p.His157Arg Uncertain significance ★★ ⚠ same type
INTS11 c.1607+18C>A Benign ★★ same type
INTS11 p.Arg196= Benign ★★ 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/ints11-p-thr182ile (accessed [today's date]).

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