Is INTS1 p.Leu1978= (c.5932C>T) pathogenic?

INTS1 p.Leu1978= (c.5932C>T) is classified Benign in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele.

INTS1 p.Leu1978=

Q: How common is INTS1 p.Leu1978= (c.5932C>T) in the general population?

INTS1 p.Leu1978= (c.5932C>T) is common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5932C>T · rs11774 · VCV792065

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.3%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.5, phastCons 1
Overall
CADD	6.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.3% African / African-American · 3,971/74,910 alleles

Filtering AF 5.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.11%

Overall 0.296% 4,747/1,606,226 alleles · common exomes 2,432/1,453,874 · genomes 2,315/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.3%	19
Admixed American	0.502%	199
Remaining individualsnot grpmax-eligible	0.389%	257
Middle Eastern	0.33%	303
South Asian	0.0256%	3,905
European (non-Finnish)	0.0163%	6,129
Finnishnot grpmax-eligible	0.00477%	20,981
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,458

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.Leu1978=
Coding: c.5932C>T
MANE Select: NM_001080453
dbSNP: rs11774
Type: single nucleotide variant
Location: chr7:1473591 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 1978: an α-helix; 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 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
INTS1 p.Ala1854Val 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-leu1978 (accessed [today's date]).

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