Is MEFV p.Pro550Ala (c.1648C>G) pathogenic?

MEFV p.Pro550Ala (c.1648C>G) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). AlphaMissense: likely benign (0.1302); Absent from gnomAD v4.1; Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Pro550Ala (c.1648C>G)?

MEFV p.Pro550Ala (c.1648C>G) is associated with familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro550Ala (c.1648C>G) in the general population?

MEFV p.Pro550Ala (c.1648C>G) is absent from gnomAD v4.1 (gnomAD).

How is Familial Mediterranean fever inherited?

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

What do computational predictors say about MEFV p.Pro550Ala (c.1648C>G)?

AlphaMissense predicts likely benign (score 0.1302) — an in-silico prediction, not a clinical call.

MEFV p.Pro550Ala

c.1648C>G · rs2141666419 · VCV1348290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1302 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial Mediterranean fever

Computational evidence

Protein change
AlphaMissense	0.1302	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	21.5	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: MEFV
Protein: p.Pro550Ala
Coding: c.1648C>G
MANE Select: NM_000243
dbSNP: rs2141666419
Type: single nucleotide variant
Location: chr16:3244551 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 550: the 'required for homotrimerization and induction of pyroptosomes' 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.Pro550= Likely benign ★★ same residue
MEFV p.Arg761His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV p.Ser242Arg Pathogenic/Likely pathogenic ★★ same condition
MEFV p.Val726Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV c.*845C>T Uncertain significance ★★ same condition
MEFV p.Ala193Thr Uncertain significance ★★ ⚠ same condition
MEFV p.Ala2Gly Uncertain significance ★★ ⚠ same condition
MEFV p.Ala416Thr 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-pro550ala (accessed [today's date]).

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