Is INTS1 p.Glu2020Lys (c.6058G>A) pathogenic?

INTS1 p.Glu2020Lys (c.6058G>A) is classified Likely benign in INTS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0998); Rare (popmax 0.209%, nfe).

How common is INTS1 p.Glu2020Lys (c.6058G>A) in the general population?

INTS1 p.Glu2020Lys (c.6058G>A) is rare (popmax 0.209%, nfe) (gnomAD).

What do computational predictors say about INTS1 p.Glu2020Lys (c.6058G>A)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

INTS1 p.Glu2020Lys

c.6058G>A · rs201873966 · VCV2657181

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.209%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.85	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 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	22.4	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 0.209% European (non-Finnish) · 2,455/1,174,212 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.199%

Overall 0.222% 3,563/1,604,448 alleles · rare exomes 3,248/1,452,080 · genomes 315/152,368 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.48%	68
European (non-Finnish)grpmax	0.209%	478
Remaining individualsnot grpmax-eligible	0.179%	559
African / African-American	0.0361%	2,773
Middle Eastern	0.0332%	3,014
South Asian	0.0321%	3,120
Admixed American	0.027%	3,711

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu2020Lys
Coding: c.6058G>A
MANE Select: NM_001080453
dbSNP: rs201873966
Type: single nucleotide variant
Location: chr7:1473084 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 2020: a UniProt-annotated variant site (in ndcagf; decreased protein abundance); a UniProt-annotated variant site (in ndcagf)

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

Similar variants

INTS1 p.Glu2020Gly Uncertain significance ★ ⚠ same residue
INTS1 c.3430-2A>C Likely pathogenic ★★ same type
INTS1 p.Arg101Ter Likely pathogenic ★★ same type
INTS1 p.Glu182Ter Likely pathogenic ★★ same type
INTS1 c.1283+5G>A Uncertain significance ★★ same type
INTS1 c.2977-5C>T Uncertain significance ★★ same type
INTS1 p.Ala1112Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1505Val 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/ints1-p-glu2020lys (accessed [today's date]).

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