Is MEFV p.Ala511= (c.1533G>A) pathogenic?

MEFV p.Ala511= (c.1533G>A) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-22). Very rare (popmax 0.004%, afr); Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Ala511= (c.1533G>A)?

MEFV p.Ala511= (c.1533G>A) is associated with familial Mediterranean fever, familial Mediterranean fever, autosomal dominant, sweet syndrome (ClinVar).

How common is MEFV p.Ala511= (c.1533G>A) in the general population?

MEFV p.Ala511= (c.1533G>A) is very rare (popmax 0.004%, afr) (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.Ala511=

c.1533G>A · rs771061550 · VCV1122743

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

familial Mediterranean fever

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 -0.58	GERP -4, phastCons 0.018
Overall
CADD	5.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,046 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00149% 24/1,614,156 alleles · very rare exomes 21/1,461,838 · genomes 3/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,015
South Asian	0.0022%	45,537
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.00144%	69,413

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.Ala511=
Coding: c.1533G>A
MANE Select: NM_000243
dbSNP: rs771061550
Type: single nucleotide variant
Location: chr16:3247070 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 511: 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

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

Also linked: familial Mediterranean fever, autosomal dominant sweet syndrome

For Familial Mediterranean fever (Orphanet):

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

Similar variants

MEFV p.Ala511Val Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Ala511Thr 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
MEFV p.Ala2Gly 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-ala511 (accessed [today's date]).

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