Is INTS9 p.Gly614Ser (c.1840G>A) pathogenic?

INTS9 p.Gly614Ser (c.1840G>A) is classified Uncertain significance in INTS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely pathogenic (0.9201); Absent from gnomAD v4.1.

How common is INTS9 p.Gly614Ser (c.1840G>A) in the general population?

INTS9 p.Gly614Ser (c.1840G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS9 p.Gly614Ser (c.1840G>A)?

AlphaMissense predicts likely pathogenic (score 0.9201) — an in-silico prediction, not a clinical call.

INTS9 p.Gly614Ser

c.1840G>A · VCV3529516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9201 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9201	likely pathogenic
REVEL	0.283	benign-leaning
SaProt	LLR -14.77	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,768 bp · p 0.25 · regional, not allelic
Overall
CADD	23.3	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

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: INTS9
Protein: p.Gly614Ser
Coding: c.1840G>A
MANE Select: NM_018250
Type: single nucleotide variant
Location: chr8:28768283 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.95 · 15 PDB
Residue 614: a β-strand

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-gly614ser (accessed [today's date]).

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