Is MEFV p.Arg501= (c.1503C>T) pathogenic?

MEFV p.Arg501= (c.1503C>T) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 8.92%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autoinflammatory syndrome.

What condition is associated with MEFV p.Arg501= (c.1503C>T)?

MEFV p.Arg501= (c.1503C>T) is associated with autoinflammatory syndrome, familial Mediterranean fever, autosomal dominant, sweet syndrome (ClinVar).

MEFV p.Arg501=

Q: How common is MEFV p.Arg501= (c.1503C>T) in the general population?

MEFV p.Arg501= (c.1503C>T) is common (popmax 8.92%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1503C>T · rs76464258 · VCV36501

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 8.92%, eas) — too common for a highly-penetrant pathogenic allele

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 -2.6	GERP -4
Overall
CADD	0.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.92% East Asian · 4,003/44,880 alleles

Filtering AF 8.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.59%

Overall 0.68% 10,980/1,614,126 alleles · common exomes 9,662/1,461,842 · genomes 1,318/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	8.92%	11
Amishnot grpmax-eligible	2.74%	36
Ashkenazi Jewishnot grpmax-eligible	1.78%	56
South Asian	1.52%	66
Remaining individualsnot grpmax-eligible	1.47%	68
Middle Eastern	0.825%	121
Admixed American	0.587%	170
African / African-American	0.396%	253
European (non-Finnish)	0.288%	347
Finnishnot grpmax-eligible	0.0297%	3,370

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.Arg501=
Coding: c.1503C>T
MANE Select: NM_000243
dbSNP: rs76464258
Type: single nucleotide variant
Location: chr16:3247100 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 501: an α-helix; 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

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

Also linked: familial Mediterranean fever, autosomal dominant sweet syndrome familial Mediterranean fever

Similar variants

MEFV p.Arg501Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Arg501Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Arg501His 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

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-arg501 (accessed [today's date]).

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