Is MEFV p.Ala511Val (c.1532C>T) pathogenic?

MEFV p.Ala511Val (c.1532C>T) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0988); Very rare (popmax 0.00517%, nfe); Associated with sweet syndrome.

What condition is associated with MEFV p.Ala511Val (c.1532C>T)?

MEFV p.Ala511Val (c.1532C>T) is associated with sweet syndrome, familial Mediterranean fever, autosomal dominant, familial Mediterranean fever (ClinVar).

How common is MEFV p.Ala511Val (c.1532C>T) in the general population?

MEFV p.Ala511Val (c.1532C>T) is very rare (popmax 0.00517%, nfe) (gnomAD).

How is Sweet syndrome inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MEFV p.Ala511Val (c.1532C>T)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

MEFV p.Ala511Val

c.1532C>T · rs144270019 · VCV646921

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sweet syndrome

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.15, phastCons 0.82
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	18.36	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

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,034 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00403% 65/1,614,040 alleles · very rare exomes 59/1,461,842 · genomes 6/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
East Asian	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,928

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.Ala511Val
Coding: c.1532C>T
MANE Select: NM_000243
dbSNP: rs144270019
Type: single nucleotide variant
Location: chr16:3247071 (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

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

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

For Sweet syndrome (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adult

Similar variants

MEFV p.Ala511= 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-ala511val (accessed [today's date]).

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