Is INTS1 p.Glu323Asp (c.969G>C) pathogenic?

INTS1 p.Glu323Asp (c.969G>C) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely benign (0.0698); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Glu323Asp (c.969G>C)?

INTS1 p.Glu323Asp (c.969G>C) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Glu323Asp (c.969G>C) in the general population?

INTS1 p.Glu323Asp (c.969G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about INTS1 p.Glu323Asp (c.969G>C)?

AlphaMissense predicts likely benign (score 0.0698) — an in-silico prediction, not a clinical call.

INTS1 p.Glu323Asp

c.969G>C · VCV4038938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0698	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	18.35	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 8.48e-05% European (non-Finnish) · 1/1,178,608 alleles

Overall 6.21e-05% 1/1,610,264 alleles · very rare exomes 1/1,458,008 · genomes 0/152,256 · joint denominator

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: INTS1
Protein: p.Glu323Asp
Coding: c.969G>C
MANE Select: NM_001080453
Type: single nucleotide variant
Location: chr7:1499143 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 323: an α-helix

Full INTS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS1 p.Glu323Gly Uncertain significance ★ ⚠ same residue
INTS1 c.1283+5G>A Uncertain significance ★★ same condition
INTS1 c.2977-5C>T Uncertain significance ★★ same condition
INTS1 p.Ala1505Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala1854Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2155Val Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala2175Thr Uncertain significance ★★ ⚠ same condition
INTS1 p.Ala4Thr Uncertain significance ★★ ⚠ same condition

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/ints1-p-glu323asp (accessed [today's date]).

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