Is IL10 p.Ala138= (c.414C>G) pathogenic?

IL10 p.Ala138= (c.414C>G) is classified Likely benign in IL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Very rare (popmax 0.005%, amr); Associated with inflammatory bowel disease.

What condition is associated with IL10 p.Ala138= (c.414C>G)?

IL10 p.Ala138= (c.414C>G) is associated with inflammatory bowel disease (ClinVar).

How common is IL10 p.Ala138= (c.414C>G) in the general population?

IL10 p.Ala138= (c.414C>G) is very rare (popmax 0.005%, amr) (gnomAD).

IL10 p.Ala138=

c.414C>G · rs771681458 · VCV1982839

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -20	GERP -5
Overall
CADD	0.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,978 alleles · very rare exomes 3/1,461,704 · genomes 0/152,274 · joint denominator

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.Ala138=
Coding: c.414C>G
MANE Select: NM_000572
dbSNP: rs771681458
Type: single nucleotide variant
Location: chr1:206769859 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 88.89 · 9 PDB
Residue 138: an α-helix

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 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
IL10 c.166-15T>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-ala138 (accessed [today's date]).

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