Is INTS11 p.Met30Leu (c.88A>T) pathogenic?

INTS11 p.Met30Leu (c.88A>T) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: ambiguous (0.3993); Very rare (popmax 0.00445%, eas).

How common is INTS11 p.Met30Leu (c.88A>T) in the general population?

INTS11 p.Met30Leu (c.88A>T) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about INTS11 p.Met30Leu (c.88A>T)?

AlphaMissense predicts ambiguous (score 0.3993) — an in-silico prediction, not a clinical call.

INTS11 p.Met30Leu

c.88A>T · VCV4038994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Computational evidence

Protein change
AlphaMissense	0.3993	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -12.24	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	24.3	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 0.00445% East Asian · 2/44,900 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,612,952 alleles · very rare exomes 2/1,460,746 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,450
European (non-Finnish)	8.48e-05%	1,179,878

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.Met30Leu
Coding: c.88A>T
MANE Select: NM_017871
Type: single nucleotide variant
Location: chr1:1321034 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 30: a β-strand

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-met30leu (accessed [today's date]).

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