Is INTS1 p.Ser1756Gly (c.5266A>G) pathogenic?

INTS1 p.Ser1756Gly (c.5266A>G) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: likely benign (0.0599); No allele count reported in gnomAD v4.1 (AN 1,579,980); Associated with Inborn genetic diseases.

What condition is associated with INTS1 p.Ser1756Gly (c.5266A>G)?

INTS1 p.Ser1756Gly (c.5266A>G) is associated with Inborn genetic diseases (ClinVar).

How common is INTS1 p.Ser1756Gly (c.5266A>G) in the general population?

INTS1 p.Ser1756Gly (c.5266A>G) is no allele count reported in gnomAD v4.1 (AN 1,579,980) (gnomAD).

What do computational predictors say about INTS1 p.Ser1756Gly (c.5266A>G)?

AlphaMissense predicts likely benign (score 0.0599) — an in-silico prediction, not a clinical call.

INTS1 p.Ser1756Gly

c.5266A>G · rs2483307214 · VCV2530263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0599 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,980)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0599	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.06	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 0.097	GERP -0.35, phastCons 0.61
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	15.51	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

No allele count reported in gnomAD v4.1 (AN 1,579,980). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: INTS1
Protein: p.Ser1756Gly
Coding: c.5266A>G
MANE Select: NM_001080453
dbSNP: rs2483307214
Type: single nucleotide variant
Location: chr7:1476341 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1756: 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 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
INTS1 p.Arg1096Cys 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-ser1756gly (accessed [today's date]).

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