Is MEFV p.Ser208fs (c.606_621dup) pathogenic?

MEFV p.Ser208fs (c.606621dup) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 2 submitters; last evaluated 2019-05-28). No gnomAD frequency available for this variant; Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Ser208fs (c.606_621dup)?

MEFV p.Ser208fs (c.606_621dup) is associated with familial Mediterranean fever (ClinVar).

How common is MEFV p.Ser208fs (c.606_621dup) in the general population?

MEFV p.Ser208fs (c.606_621dup) is no gnomAD frequency available for this variant (gnomAD).

How is Familial Mediterranean fever inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MEFV p.Ser208fs

c.606_621dup · rs104895180 · VCV97533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial Mediterranean fever

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, 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: MEFV
Protein: p.Ser208fs
Coding: c.606_621dup
MANE Select: NM_000243
dbSNP: rs104895180
Type: Duplication
Location: chr16:3254446 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 208: the 'disordered' region

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

Disease context

familial Mediterranean fever — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial Mediterranean fever (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: >1 / 1000 (Turkey)

Similar variants

MEFV p.Ser208Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Ser503fs Likely pathogenic ★★ same condition
MEFV p.Asn256fs Uncertain significance ★★ same condition
MEFV p.Glu148fs Uncertain significance ★★ same condition
MEFV p.Ala220fs Conflicting classifications of pathogenicity ★ same condition
MEFV p.Gln370fs Uncertain significance ★ same condition
MEFV p.Gln778fs Uncertain significance ★ same condition
MEFV p.Glu200fs Uncertain significance ★ 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/mefv-p-ser208fs (accessed [today's date]).

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