Is IL6 p.Pro32Ser (c.94C>T) pathogenic?

IL6 p.Pro32Ser (c.94C>T) is classified Benign in IL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0775); Common (popmax 8.3%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about IL6 p.Pro32Ser (c.94C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

IL6 p.Pro32Ser

Q: How common is IL6 p.Pro32Ser (c.94C>T) in the general population?

IL6 p.Pro32Ser (c.94C>T) is common (popmax 8.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.94C>T · rs2069830 · VCV768143

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.095	GERP -4
Regional constraint	o/e 1.06	unconstrained · MANE · 4,307 bp · p 0.34 · regional, not allelic
Overall
CADD	7.235	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.3% African / African-American · 6,227/75,022 alleles

Filtering AF 8.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.06%

Overall 0.446% 7,197/1,613,924 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.3%	12
Remaining individualsnot grpmax-eligible	0.605%	165
Admixed American	0.603%	166
Middle Eastern	0.379%	264
South Asian	0.0253%	3,958
European (non-Finnish)	0.0156%	6,413

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: IL6
Protein: p.Pro32Ser
Coding: c.94C>T
MANE Select: NM_000600
dbSNP: rs2069830
Type: single nucleotide variant
Location: chr7:22727518 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 86.05 · 17 PDB
Residue 32: a UniProt-annotated variant site (in)

Full IL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL6 p.Asp162Val Benign ★★ same type
IL6 p.Leu61= Likely benign ★★ same type
IL6 p.Ser65= Likely benign ★★ same type
IL6 p.Ala40Asp Uncertain significance ★ ⚠ same type
IL6 p.Arg141Ile Uncertain significance ★ ⚠ same type
IL6 p.Arg196Ser Uncertain significance ★ ⚠ same type
IL6 p.Arg207Thr Uncertain significance ★ ⚠ same type
IL6 p.Asn183Lys 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/il6-p-pro32ser (accessed [today's date]).

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