Is IL6 p.Arg207Thr (c.620G>C) pathogenic?

IL6 p.Arg207Thr (c.620G>C) is classified Uncertain significance in IL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-22). AlphaMissense: likely pathogenic (0.8987); Absent from gnomAD v4.1.

How common is IL6 p.Arg207Thr (c.620G>C) in the general population?

IL6 p.Arg207Thr (c.620G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IL6 p.Arg207Thr (c.620G>C)?

AlphaMissense predicts likely pathogenic (score 0.8987) — an in-silico prediction, not a clinical call.

IL6 p.Arg207Thr

c.620G>C · rs2534043271 · VCV2303034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8987	likely pathogenic · top 5% in IL6
REVEL	0.509	indeterminate
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,307 bp · p 0.34 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IL6
Protein: p.Arg207Thr
Coding: c.620G>C
MANE Select: NM_000600
dbSNP: rs2534043271
Type: single nucleotide variant
Location: chr7:22731554 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 86.05 · 17 PDB
Residue 207: an α-helix

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.Asn183Lys Uncertain significance ★ ⚠ same type
IL6 p.Asn73Ser 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-arg207thr (accessed [today's date]).

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