Is IL6ST p.Phe613fs (c.1834_1835dup) pathogenic?

IL6ST p.Phe613fs (c.18341835dup) is classified Pathogenic in IL6ST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-29). No gnomAD frequency available for this variant.

How common is IL6ST p.Phe613fs (c.1834_1835dup) in the general population?

IL6ST p.Phe613fs (c.1834_1835dup) is no gnomAD frequency available for this variant (gnomAD).

IL6ST p.Phe613fs

c.1834_1835dup · rs2533477589 · VCV2131727

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.81	GERP -0.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IL6ST
Protein: p.Phe613fs
Coding: c.1834_1835dup
MANE Select: NM_002184
dbSNP: rs2533477589
Type: Duplication
Location: chr5:55951468 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 20 PDB
Residue 613: the fibronectin type-iii 5 domain; a UniProt-annotated variant site (in stws2; results in impaired cytokine-mediated signaling pathway with loss of response to il-6, il-11, il-27, osm and lif; does not localize to the cell membrane)

Full IL6ST gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL6ST p.Phe613= Uncertain significance ★ same residue
IL6ST p.Ser731fs Pathogenic ★★ same type
IL6ST c.1268-25_1268-18dup Likely benign ★★ same type
IL6ST c.1841-4dup Benign/Likely benign ★★ same type
IL6ST c.1841-6_1841-4dup Benign/Likely benign ★★ same type
IL6ST c.1841-7_1841-4dup Likely benign ★★ same type
IL6ST p.Ile719fs Pathogenic ★ same type
IL6ST c.1841-2dup 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/il6st-p-phe613fs (accessed [today's date]).

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