Is IL1A p.Pro211Ser (c.631C>T) pathogenic?

IL1A p.Pro211Ser (c.631C>T) is classified Uncertain significance in IL1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.8078); Very rare (popmax 0.00133%, afr).

How common is IL1A p.Pro211Ser (c.631C>T) in the general population?

IL1A p.Pro211Ser (c.631C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about IL1A p.Pro211Ser (c.631C>T)?

AlphaMissense predicts likely pathogenic (score 0.8078) — an in-silico prediction, not a clinical call.

IL1A p.Pro211Ser

c.631C>T · rs1206066536 · VCV3109226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8078	likely pathogenic · top 8% in IL1A
REVEL	0.315	indeterminate
SaProt	LLR -11.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 8,700 bp · p 0.79 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,046 alleles

Overall 6.2e-05% 1/1,613,712 alleles · very rare exomes 1/1,461,362 · genomes 0/152,350 · 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: IL1A
Protein: p.Pro211Ser
Coding: c.631C>T
MANE Select: NM_000575
dbSNP: rs1206066536
Type: single nucleotide variant
Location: chr2:112775252 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.49 · 4 PDB

Full IL1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL1A p.Asp138Asn Benign ★★ same type
IL1A p.Ile92= Benign ★★ same type
IL1A p.Thr153= Likely benign ★★ same type
IL1A p.Ala238Val Uncertain significance ★ ⚠ same type
IL1A p.Ala245Asp Uncertain significance ★ ⚠ same type
IL1A p.Asn121Ser Uncertain significance ★ ⚠ same type
IL1A p.Asn141Ser Uncertain significance ★ ⚠ same type
IL1A p.Asn148Thr 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/il1a-p-pro211ser (accessed [today's date]).

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