Is IL10 p.His2= (c.6C>T) pathogenic?

IL10 p.His2= (c.6C>T) is classified Likely benign in IL10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). Ultra-rare (popmax 0.0166%, mid); Associated with inflammatory bowel disease.

What condition is associated with IL10 p.His2= (c.6C>T)?

IL10 p.His2= (c.6C>T) is associated with inflammatory bowel disease (ClinVar).

How common is IL10 p.His2= (c.6C>T) in the general population?

IL10 p.His2= (c.6C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

IL10 p.His2=

c.6C>T · rs140486772 · VCV1131513

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

inflammatory bowel disease

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 2.4	GERP -1.1, phastCons 0.98
Overall
CADD	9.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,010 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00409% 66/1,614,094 alleles · ultra-rare exomes 64/1,461,730 · genomes 2/152,364 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,010
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00441%	22,693
Admixed American	0.00333%	30,016
South Asian	0.00329%	30,359

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: IL10
Protein: p.His2=
Coding: c.6C>T
MANE Select: NM_000572
dbSNP: rs140486772
Type: single nucleotide variant
Location: chr1:206772430 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 88.89 · 9 PDB

Full IL10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inflammatory bowel disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IL10 p.His2Arg Uncertain significance ★ ⚠ same residue
IL10 c.225+6A>G Uncertain significance ★★ same condition
IL10 p.Arg124Trp Uncertain significance ★★ ⚠ same condition
IL10 p.Arg177Ter Uncertain significance ★★ same condition
IL10 p.Glu169Asp Uncertain significance ★★ ⚠ same condition
IL10 p.Leu13Met Uncertain significance ★★ ⚠ same condition
IL10 c.165+20G>A Likely benign ★★ same condition
IL10 c.165+8T>C Benign/Likely benign ★★ 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/il10-p-his2 (accessed [today's date]).

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