Is INTS1 p.Ser186= (c.558C>T) pathogenic?

INTS1 p.Ser186= (c.558C>T) is classified Likely benign in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Rare (popmax 0.163%, afr).

How common is INTS1 p.Ser186= (c.558C>T) in the general population?

INTS1 p.Ser186= (c.558C>T) is rare (popmax 0.163%, afr) (gnomAD).

INTS1 p.Ser186=

c.558C>T · VCV4894979

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.163%, afr)

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 5.1	GERP -1.3, phastCons 1
Overall
CADD	7.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% African / African-American · 122/75,056 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.00812% 131/1,613,360 alleles · rare exomes 52/1,461,024 · genomes 79/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.163%	615
Remaining individualsnot grpmax-eligible	0.008%	12,495
Admixed American	0.00667%	15,002

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.Ser186=
Coding: c.558C>T
MANE Select: NM_001080453
Type: single nucleotide variant
Location: chr7:1500010 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 186: an α-helix

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

Similar variants

INTS1 p.Ser186Asn Uncertain significance ★ ⚠ same residue
INTS1 p.Ser186Cys 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

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-ser186 (accessed [today's date]).

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