Is INTS6 p.Gly30Val (c.89G>T) pathogenic?

INTS6 p.Gly30Val (c.89G>T) is classified Uncertain significance in INTS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely pathogenic (0.7438); Absent from gnomAD v4.1.

How common is INTS6 p.Gly30Val (c.89G>T) in the general population?

INTS6 p.Gly30Val (c.89G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS6 p.Gly30Val (c.89G>T)?

AlphaMissense predicts likely pathogenic (score 0.7438) — an in-silico prediction, not a clinical call.

INTS6 p.Gly30Val

c.89G>T · VCV3860856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7438 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7438	likely pathogenic
REVEL	0.399	indeterminate
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 57 kb · p 2.7e-18 · regional, not allelic
Overall
CADD	32.0	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: INTS6
Protein: p.Gly30Val
Coding: c.89G>T
MANE Select: NM_012141
Type: single nucleotide variant
Location: chr13:51452437 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.80 · 9 PDB
Residue 30: the vwfa domain; an α-helix

Full INTS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SERPINE3 p.Lys30Arg Uncertain significance ★ ⚠ same residue
INTS6 p.Gly30= Uncertain significance same residue
INTS6 p.Thr749Ala Benign ★★ same type
INTS6 p.Arg206Cys Likely pathogenic ★ same type
INTS6 p.Arg610Ter Pathogenic ★ same type
INTS6 p.Gln185Ter Pathogenic ★ same type
INTS6 p.Gln228Glu Likely pathogenic ★ same type
INTS6 c.613+2T>C 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/ints6-p-gly30val (accessed [today's date]).

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