Is IL10 p.Ser111Phe (c.332C>T) pathogenic?

IL10 p.Ser111Phe (c.332C>T) is classified Uncertain significance in IL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-27). AlphaMissense: likely benign (0.1469); Very rare (popmax 0.0022%, sas); Associated with inflammatory bowel disease.

What condition is associated with IL10 p.Ser111Phe (c.332C>T)?

IL10 p.Ser111Phe (c.332C>T) is associated with inflammatory bowel disease (ClinVar).

How common is IL10 p.Ser111Phe (c.332C>T) in the general population?

IL10 p.Ser111Phe (c.332C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about IL10 p.Ser111Phe (c.332C>T)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

IL10 p.Ser111Phe

c.332C>T · rs1674812448 · VCV1004415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

inflammatory bowel disease

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 3,796 bp · p 0.00037 · regional, not allelic
Overall
CADD	19.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,614,126 alleles · very rare exomes 2/1,461,850 · genomes 0/152,276 · 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.Ser111Phe
Coding: c.332C>T
MANE Select: NM_000572
dbSNP: rs1674812448
Type: single nucleotide variant
Location: chr1:206770953 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 88.89 · 9 PDB
Residue 111: 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-ser111phe (accessed [today's date]).

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