Is MEFV p.Pro50= (c.150G>A) pathogenic?

MEFV p.Pro50= (c.150G>A) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0121%, sas); Associated with autoinflammatory syndrome.

What condition is associated with MEFV p.Pro50= (c.150G>A)?

MEFV p.Pro50= (c.150G>A) is associated with autoinflammatory syndrome, familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro50= (c.150G>A) in the general population?

MEFV p.Pro50= (c.150G>A) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

MEFV p.Pro50=

c.150G>A · rs376952748 · VCV1079935

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.1	GERP -4.2
Overall
CADD	0.527	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,086 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00341% 55/1,614,238 alleles · ultra-rare exomes 49/1,461,886 · genomes 6/152,352 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,281
African / African-American	0.00666%	15,013
Admixed American	0.005%	20,008
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.0028%	35,759

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: MEFV
Protein: p.Pro50=
Coding: c.150G>A
MANE Select: NM_000243
dbSNP: rs376952748
Type: single nucleotide variant
Location: chr16:3256438 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 50: the pyrin domain; a turn

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

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial Mediterranean fever

Similar variants

MEFV p.Pro50Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Pro50Ala Uncertain significance ★ ⚠ same residue
MEFV p.Pro50Thr Uncertain significance ★ ⚠ 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

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-pro50 (accessed [today's date]).

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