Is INTS9 p.Thr88Met (c.263C>T) pathogenic?

INTS9 p.Thr88Met (c.263C>T) is classified Uncertain significance in INTS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.0644); Ultra-rare (popmax 0.0176%, sas).

How common is INTS9 p.Thr88Met (c.263C>T) in the general population?

INTS9 p.Thr88Met (c.263C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about INTS9 p.Thr88Met (c.263C>T)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

INTS9 p.Thr88Met

c.263C>T · rs368909488 · VCV2265073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 93 kb · p 0.36 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0176% South Asian · 16/90,940 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.009%

Overall 0.0031% 50/1,611,978 alleles · ultra-rare exomes 47/1,459,844 · genomes 3/152,134 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,684
African / African-American	0.00534%	18,711
Admixed American	0.00334%	29,958
European (non-Finnish)	0.00238%	42,094

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: INTS9
Protein: p.Thr88Met
Coding: c.263C>T
MANE Select: NM_018250
dbSNP: rs368909488
Type: single nucleotide variant
Location: chr8:28837775 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.95 · 15 PDB

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.Ala286Asp 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

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-thr88met (accessed [today's date]).

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